RNA Viruses

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RNA Viruses with examples of diseases

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 Enveloped Segmented SS RNA
Viruses includs:

• Orthomyxoviruses - Influenza

• Bunyaviruses - Hantavirus

• Arenaviruses - California encephalitis

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 Orthomyxoviridae

• -ssRNA linear genome

• It contains 8 segmented
genomes, coding for
proteins.

• Site of replication is
nucleus

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 Influenza viruses
• Influenza A virus: Humans, Animals and birds

• Influenza B virus Only humans

• Influenza C virus Only humans

• Antigenic changes continuously in type A

• Lesser degree Group B-sometimes epidemics

• Type C antigenically stable

 No X reactivity among 3 types

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 Influenza type A

• Infect a wide variety of mammals, including man,

pigs, & birds.
• The main human pathogen, associated with
epidemics & pandemics!.
• Pigs & birds are important reservoirs, generating
pools of diverse viruses which get transferred
back to the human population.
• Close contact between pigs & man!!

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 Influenza A viruses Classification

• Influenza A virus subtypes based on antigenic differences

in HA and NA glycoproteins
• There are 17 known haemagglutinin (H) serotypes
• 9 known neuraminidase (N) serotypes.
– H1-H17

– N1-N9

=>H3N2

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Structure of Influenza A virus

Type C has 7=>lacking NA gene

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 Nomenclature

• Name of influenza virus strain includes:

 Type

 Host of origin

 Geographic origin

 Strain number

 Date of original isolation

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 Nomenclature

 Antigenic description of HA and NA in parenthese for type A

 Host of origin not in human isolates

• E.g., a current strain of influenza virus might be designated

A/Bangkok/1/79 (H3N2),

Meaning that it is an influenza A virus that was first

isolated in Bangkok in 1979 and contains HA
(H3) and NA (N2) antigens.

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 Nomenclature
• Strains of influenza B are designated by:
 Type,

 Geography, and

 Date of isolation

e.g., B/Singapore/3/64, but without specific mention of

HA or NA antigens, because no antigenic shift or
pandemics as does influenza A.

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 Transmission

 Virus is spread by inhalation of small aerosol

droplets expelled during talking, breathing, and
coughing

 Virus likes a cool, less humid atmosphere (e.g.,

winter heating season)

 Virus is extensively spread by school children

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 TRANSMISSION

• AEROSOL
– 100,000 TO 1,000,000
VIRIONS PER
DROPLET
• SURFACES
- VIRUS CAN SURVIVE
APPROX 2 TO 8 HRS
• 18-72 HR
INCUBATION

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 Risk group

 High-risk groups:
o Elderly and immunocompromised people

o People in nursing homes

o Underlying cardiac

o Respiratory problems (including asthma sufferers and

smokers

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 Pathogenesis

• Influenza initially establishes a local upper

respiratory tract infection

• The virus first targets and kills mucus-secreting, ciliated,

and other epithelial cells,
=>causing the loss of this primary defense system

• NA cleaves sialic acid (neuraminic acid) residues of

the mucus, thereby providing access to tissue.

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 Pathogenesis cotn’d….

• Cell-to-cell spread and transmission to other hosts.

• Spreads to the lower respiratory tract,

Causes severe desquamation (shedding) of

bronchial or alveolar epithelium down to a
single-cell basal layer or to the basement
membrane.

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Pathogenesis cotn’d….

• Promotes bacterial adhesion to the epithelial cells

• Pneumonia may result from a viral pathogenesis

or from a secondary bacterial infection.

• Influenza may also cause a transient or low-level

viremia but rarely involves tissues other than the
lung.

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Pathogenesis

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 Antigenic Drift

• Minor antigenic changes in HA and NA → antigenic

drift

• Accumulate mutations in gene → AA changes in

protein

– Escape recognition of host’s IR

• Immune response no longer protects fully

• Sporadic outbreaks, limited epidemics

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 ANTIGENIC DRIFT

• HA and NA accumulate mutations

– RNA virus

• Immune response no longer protects fully

• Sporadic outbreaks, limited epidemics

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 Antigenic Shift

• Major/drastic antigenic changes in HA and NA

• Genetic reassortment especially doubly infected cells

• Not in Type B and C

• “new” HA or NA proteins

• Pre-existing antibodies do not protect

• May get pandemics

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 ANTIGENIC SHIFT
• “New” HA or NA proteins

• Pre-existing antibodies do not protect

• May get pandemics

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Antigenic
Shift
H2N2
H1N1

H1N1 * H2N2

H2N1 OR H1N2

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Where do “new” HA and NA come from?

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 Why do we not have influenza B
pandemics?

• So far no shifts
have been
recorded

• No animal
reservoir known

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 Influenza Pandemics =>Antigenic Shift

• Influenza is one of the most prevalent and significant

viral infections.

• The most famous influenza pandemic (worldwide) is the

Spanish influenza that swept the world in 1918 to
1919, killing 20 to 40 million people.

More people died of influenza during that time than

in the battles of WW-I.

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 Influenza Pandemics

Year of Pandemic Influenza A Subtype

1918 H1N1

1947 H1N1

1957 H2N2; Asian flu strain

1968 H3N2; Hong Kong flu strain

1977 H1N1; Russian

1997, 2003 H5N1: China, Avian

2009 H1N1, Swine flu

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 Clinical Syndromes

• IP of 1 to 4 days=> “flu syndrome” begins with a brief

prodrome of malaise and headache lasting a few hours.

• Followed by the abrupt onset of fever, chills, severe

Myalgias, loss of appetite, weakness and fatigue, sore throat,
and usually a nonproductive cough.

• The fever persists for 3 to 8 days, and unless a complication

occurs, recovery is complete within 7 to 10 days.

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 Clinical Syndromes

• Complications of influenza virus infection

 Primary viral pneumonia

 Secondary bacterial pneumonia

 Myositis and cardiac involvement

 Neurologic syndromes:

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 Pulmonary Complications

• Croup (Young Children)

• Primary Influenza Virus Pneumonia
• Secondary Bacterial Infection
– Streptococcus pneumoniae
– Staphlyococcus aureus
– Hemophilus influenzae

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 Non-pulmonary complications

• Myositis (rare, > in children, > with type B)

• Cardiac complications
• Encephalopathy
• Liver and CNS
– Reye’s syndrome

• Peripheral nervous system

– Guillian-Barré syndrome

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 MORTALITY

• MAJOR CAUSES OF INFLUENZA VIRUS-

ASSOCIATED DEATH
– BACTERIAL PNEUMONIA
– CARDIAC FAILURE

• 90% OF DEATHS IN THOSE OVER 65 YEARS

OF AGE

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 Laboratory Diagnosis

• The diagnosis=> characteristic symptoms, the season,

and the presence of the virus in the community.

• Laboratory methods that distinguish influenza from

other respiratory viruses and identify its type and strain
confirm the diagnosis

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 Laboratory Diagnosis

• Culture

• Serology

• PCR

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 Prevention and Control

• The airborne spread of influenza is almost impossible to limit.

• However, the best way to control the virus is through

immunization.

• Natural immunization, which results from prior exposure, is

protective for long periods.

• A killed-virus vaccine representing the “strains of the year”

and antiviral drug prophylaxis can also prevent infection

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 VACCINE

• ‘BEST GUESS’ OF MAIN ANTIGENIC

TYPES
– CURRENTLY SEASONAL VACCINE TRIVALENT
• type A - H1N1
• type A - H3N2
• type B
• each year choose which strain of each subtype is the
best to use for optimal protection

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 usual timing – 2009 rather
different

CDC

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 PREVENTION - DRUGS

• RIMANTADINE (M2)
• Type A only

• AMANTADINE (M2)
• Type A only

Needs to be given early!

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Paramyxoviridae

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 Paramyxoviridae
• -ss RNA
• A helical nucleocapsid
• Enveloped
• Are larger and do not have
the segmented genome.
• Two glycoproteins:
 a fusion (F) protein
 Protein (hemagglutinin-
neuraminidase [HN],
hemagglutinin [H],or
glycoprotein [G]protein)

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 Paramyxoviridae

Genus Human Pathogen

Morbillivirus Measles virus

Paramyxovirus Parainfluenzaviruses 1 to 4
Mumps virus

Pneumovirus Respiratory syncytial virus (RSV)

Metapneumovirus

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 Unique Features
• The three genera can be distinguished by the
activities of the viral attachment protein:
 HN of parainfluenza virus and mumps virus binds to sialic
acid and has hemagglutinin and neuraminidase activity,

 H of measles virus binds protein receptors and is also a

hemagglutinin,

 G of RSV binds but is not a hemagglutinin.

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 Unique features cotn’d…

• Penetrate the cell by fusion with the plasma membrane

• Exit by budding from the plasma membrane.

• Induce cell-to-cell fusion

• Transmitted in respiratory droplets and initiate infection

in the respiratory tract.

• CMI causes many of the symptoms

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MEASLES VIRUS

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 MEASLES VIRUS

• Measles, also known as rubeola

• One of the five classic childhood exanthems

• Rubella, roseola, fifth disease, and chickenpox.

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 Pathogenesis

• Contagious - respiratory droplets

• Local replication of virus in epithelial cells of the
respiratory tract
• Infects monocytes and lymphocytes, and the virus is
spread through the lymphatic system and by a cell-
associated viremia=>Increases risk to opportunistic
and other infections

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 Pathogenesis cotn’d….

• The characteristic maculopapular measles rash=>

immune T cells targeted to measles-infected
endothelial cells.

• Recovery follows the rash in most patients

 Who then have lifelong immunity to the virus.

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 Pathogenesis cotn’d….

• Formation of giant cells

• Escape antibody control.

• Inclusions occur most commonly in the cytoplasm-

composed of incomplete viral particles.

• Virus production occurs with eventual cell lysis.

• Persistent infections without lysis can occur in

certain cell types (e.g., human brain cells).

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 Pathogenesis cotn’d….

• Measles can cause encephalitis in three ways:

Direct infection of neurons;

A post-infectious encephalitis, which is believed to be

immune mediated; and

Subacute sclerosing panencephalitis (SSPE) caused

by a defective variant of measles generated during the
acute disease.

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 Pathogenesis cotn’d….

• T-cell–deficient children atypical presentation, consisting

of giant cell pneumonia without a rash.

• Antibody, including maternal antibody and passive

immunization, can block the viremic spread of the virus and
prevent or lessen disease.

• Protection from reinfection is lifelong.

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Mechanisms of spread of the measles virus

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 Clinical Syndromes: Measles

• Measles is a serious febrile illness

• The incubation period lasts 7 to 13 days, and the

prodrome starts with high fever and “CCC and P”—
cough, coryza, conjunctivitis, and photophobia.

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 Clinical features

• 3 Cs (Cough, Coryza &

Conjunctivitis)

• Koplik spots

• Four days fever (400c)

• Generalized, maculopapular,erythem

atous rash.

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Clinical
Syndromes:
Measles Rash

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 Clinical Syndromes: Koplik Spots

• Small bluish-white spots on a red background found in

the buccal mucosa inside the cheek near the 2nd molars

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 Complication: Pneumonia

• Can also be a serious complication, accounts for

60% of the deaths caused by measles.

• Mortality is associated with pneumonia is higher in

the malnourished and for the extremes of age.

• Bacterial super-infection is common in patients

with pneumonia caused by the measles virus.

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 Complication: Encephalitis

• One of the most feared complications of measles

• Occurs in as few as 0.5% of those infected but

carries a fatality rate of 15%.

• Caused by immunopathologic reactions, associated with

demyelination of neurons, and occurs more often in
older children and adults.
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 Complication: Subacute Sclerosing
Panencephalitis (SSPE)
• Very late neurologic sequela of measles that
afflicts approximately 7 of every 1 million
patients.
• The incidence decreased because vaccination
programs.
• =>defective measles virus persists in the
brain, and acts as a slow virus.

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Time

course of

measles

virus

infection

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 Epidemiology of Measles

 Host range limited to humans

 Only one serotype exists
• Transmission
 Inhalation of large-droplet aerosols
• Who Is at Risk?
 Unvaccinated people
 Malnourished people, who have more serious outcomes
 Immunocompromised people, who have more serious outcomes
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 Laboratory Diagnosis: Measle

• Characteristic CPE, including multinucleated giant cells

with cytoplasmic inclusion bodies

Giemsa stained cells taken from the upper respiratory

tract and urinary sediment
• Antibody, especially immunoglobulin M (IgM), can be
detected when the rash is present.

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 MMR Vaccine

• Composition: live attenuated viruses

• Efficiency: 95% lifelong immunization with a

single dose

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MUMPSVIRUS

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 Pathogenesis

• Virus infects epithelial cells of respiratory tract.

• Virus spreads systemically by viremia.

• Infection of parotid gland, testes, and central nervous system

occurs

• Principal symptom is swelling of parotid glands caused by

inflammation.

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Pathogenesis cotn’d…..

• CMI is essential for control of infection and responsible

for causing some of the symptoms.
• Antibody is not sufficient because of virus’s ability to
spread cell to cell.
 Host range is limited to humans
 Only one serotype exists
 Immunity is lifelong

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Mechanism of spread of mumps virus within the
body

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 Mumps
• Mumps infections are
often asymptomatic.
• Clinical illness manifests
as a parotitis that is almost
always bilateral and
accompanied by fever.
• Onset is sudden.

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 Complication: Mumps

• The swelling that results from mumps oorchitis may

cause sterility.

• Mumps virus involves the CNS in approximately

50% of patients; 10% of those affected may
exhibit mild meningitis with 5 per 1000 cases of
encephalitis.

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Time course of mumps virus infection

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 Laboratory Diagnosis

• Sipecimens: saliva, urine, the pharynx, secretions

from the Stensen duct, and cerebrospinal fluid.

• Culture

• Serology

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 MMR Vaccine

• Composition: live attenuated viruses

• Efficiency: 95% lifelong immunization with a single

dose

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Parainfluenza Viruses

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 Para-influenzaviruses
• Are respiratory viruses that usually cause mild cold like
symptoms but can also cause serious respiratory tract
disease.

• Four serologic types within the parainfluenza genus are

human pathogens.

• Types 1, 2, and 3 are second only to RSV as important

causes of severe lower respiratory tract infection in
infants and young children.

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 Pathogenesis

• They are especially associated with

laryngotracheobronchitis (croup)

• Infection is limited to the respiratory tract; upper

respiratory tract disease is most common, but
significant disease can occur with lower respiratory
tract infection.

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Pathogenesis cotn’d….

• Parainfluenza viruses do not cause viremia or

become systemic.
• Diseases include cold likes symptoms, bronchitis
(inflammation of bronchial tubes), and croup
(laryngotracheobronchitis).
• Infection induces protective immunity of short
duration.

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 Transmission

 Inhalation of large-droplet aerosols

Who Is at Risk?

 Children: at risk for mild disease or croup

 Adults: at risk for reinfection with milder symptoms

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 Clinical Syndromes

• A mild cold like upper respiratory tract infection

(coryza, pharyngitis, mild bronchitis, wheezing,
and fever) to bronchiolitis and pneumonia.

• Older children and adults generally experience milder

infections than those seen in young children, although
pneumonia may occur in the elderly.

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 Clinical Syndromes

• Hoarseness, a “seal bark” cough, tachypnea,

tachycardia, and suprasternal retraction develop
in infected patients after a 2- to 6-day incubation
period.
• Most children recover within 48 hours.
• The principal differential diagnosis is epiglottitis
caused by Haemophilus influenzae.

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 Laboratory Diagnosis

• Isolated from nasal washings and respiratory

secretions and grows well in primary monkey kidney
cells

• Indicated by the finding => syncytia

• RT-PCR

• The serotype of the virus can be determined through

the use of specific antibody
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 Prevention, and Control

• No vaccine is available.

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Respiratory Syncytial

Virus

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 Respiratory Syncytial Virus

• First isolated from a chimpanzee in 1956, is a member of

the Pneumovirus genus.

• Unlike the other paramyxoviruses, RSV lacks a hemagglutinin.

• The most common cause of fatal acute respiratory tract infection

in infants and young children.

• Children 6 months of age or younger are especially susceptible to

serious disease of the respiratory tract.

• Reinfections occur throughout life, even among elderly

persons.
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 Pathogenesis and Immunity
• Virus causes localized infection of respiratory tract.
• Virus does not cause viremia or systemic spread.
• Pneumonia results from cytopathologic spread of virus
(including syncytia).
• Bronchiolitis is most likely mediated by host’s immune
response.
• Necrosis of the bronchi and bronchioles leads to the formation
of “plugs” of mucus, fibrin, and necrotic material within smaller
airways.

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 Laboratory Diagnosis

• RSV is difficult to isolate in cell culture.

• The presence of the viral genome in infected

cells and nasal washings can be detected by
RT-PCR techniques

• A fourfold or greater increase in the antibody

titer can confirm the diagnosis for
epidemiologic purposes.
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 Prevention and Control
• Passive immunization with anti-RSV immunoglobulin
is available for premature infants.

• Infected children must be isolated.

• Infection-control measures are required for hospital

staff caring for infected children include:

Hand washing

Wearing gowns, goggles, and masks.

• No vaccine is currently available for RSV prophylaxis.

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Summary

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Virology, 2023 87
 Rhabdoviruses

 Greek word rhabdos, meaning =>“rod”

 Pathogens for a variety of mammals, birds, and
plants.
 The most significant pathogen of the
rhabdoviruses=>rabies virus
• Until Louis Pasteur developed the killed-rabies vaccine, a
bite from a “mad” dog always led to the characteristic
symptoms of hydrophobia and certain death.

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 Structure

• Bullet-shaped, enveloped,
• -ssRNA, helical nucleocapsid
• Diameter of 50 to 95 nm and length
of 130 to 380 nm
• Spikes composed of glycoprotein
(G) cover the surface of the virus.
• The viral attachment protein, G
protein, generates neutralizing
antibodies.

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 Transmission

• Infection usually results from the bite of a rabid

animal.

• Infection of the animal causes

• Secretion of the virus in the animal’s saliva.

• The virus can also be transmitted through

– The inhalation of aerosolized virus (as may be found in
bat caves),

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Virology, 2023 91
 Pathogenesis: Rabies Virus

• The viral G protein attaches to the host cell and is

internalized by endocytosis.
• Rabies virus binds to either the nicotinic acetylcholine
receptor (AChR), neural cell adhesion molecule
(NCAM), or other molecules.
• The virus replicates quietly at the site of infection for
days to months =>PNS=>CNS
• Rabies virus travels=> dorsal root ganglia and the spinal
cord=> the brain becomes rapidly infected => virus
production increases.
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Pathogenesis: Rabies Virus cotn’d…

• Disseminates from the CNS =>to highly innervated

sites such as the skin of the head and neck, salivary
glands, retina, cornea, nasal mucosa…
• Virus is released efficiently from the salivary gland=>
promote contagion
• Encephalitis develops and neurons degenerate.
• The affected tissue=>presence of Negri bodies
• Rabies is fatal once clinical disease is apparent.

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 Pathogenesis cotn’d…

• Pathogenesis of
rabies virus
infection.
• Numbered steps
describe the
sequence of events

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Virology, 2023 95
Pathogenesis cotn’d…

• The length of the IP is determined by

1. The concentration of the virus in the inoculum,

2. The proximity of the wound to the brain,

3. The severity of the wound,

4. The host’s age, and

5. The host’s immune status.

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Pathogenesis cotn’d…

• Neutralizing antibodies are not apparent until after the

clinical disease is well established.
• The infection remains hidden from the immune
response.
• CMI appears to play little or no role in protection against
rabies virus infection.
• Antibody can block the spread of virus to the CNS and
brain =>if administered or generated during the IP.
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 Epidemiology: Rabies Virus

• Classic zoonotic infection

• Accounts for 70,000 deaths, mostly children, annually

worldwide.

• At least 25,000 deaths in India

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 Epidemiology: Rabies Virus
• Who Is at Risk?

 Veterinarians and animal handlers

 Person bitten by a rabid animal

 Inhabitants of countries with no pet vaccination program

• Geography/Season

 Virus found worldwide, except in some island nations

 No seasonal incidence

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 Progression of Rabies Disease

• Always fatal unless treated by vaccination.

• After a long but highly variable incubation period, the
prodrome phase of rabies ensues.
1. Incubation phase
• Symptoms: Asymptomatic
• Time (Days): 60-365 after bite
• Viral Status: Low titer, virus in muscle
• Immunologic Status: -----

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 Progression of Rabies Disease

2. Prodrome phase

• Symptoms: Fever, nausea, vomiting, loss of appetite,

headache, lethargy, pain at site of bite

• Time (Days): 2-10

• Viral Status: Low titer, virus in CNS and brain

• Immunologic Status: -----

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 Progression of Rabies Disease
3. Neurologic phase

• Symptoms: hydrophobia, pharyngeal spasms, hyperactivity,

anxiety, depression

CNS symptoms: loss of coordination, paralysis,

confusion, delirium
• Time (Days): 2-7

• Viral Status: high titer, virus in brain and other sites

• Immunologic Status: Detectable antibody in serum and CNS

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 Progression of Rabies Disease
4. Coma

• Symptoms: Coma, hypotension, hypoventilation, secondary

infections, cardiac arrest

• Time (Days): 0-14

• Viral Status: high titer, virus in brain and other sites

• Immunologic Status: ------

5. Death

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Neurologic phase

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Clinical summary

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 Laboratory Diagnosis

• The occurrence of neurologic symptoms in a person,

bitten by an animal, generally establishes the
diagnosis of rabies.

• Unfortunately, evidence of infection, including symptoms

and the detection of antibody, does not occur until it is too
late for intervention.

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 Laboratory Diagnosis
• The diagnosis of rabies is made through
 detection of viral antigen in the CNS or skin,

 isolation of the virus,

 detection of the genome, and

 serologic findings.

• The hallmark diagnostic finding has been the detection

of intracytoplasmic inclusions consisting of aggregates of
viral nucleocapsids (Negri bodies) in affected neurons

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 Diagnosis of Rabies Virus

Adelchi Negri, an assistant pathologist

Virology, 2023 108

 Prophylaxis

• Postexposure prophylaxis is the only hope for preventing

overt clinical illness in the affected person, human rabies
immunoglobulin (HRIG).
• Prophylaxis should be initiated for anyone exposed
 By bite or by contamination of an open wound
 Mucous membrane to the saliva
 Brain tissue of an animal suspected to be infected with the
virus,
• Unless the animal is tested and shown not to be rabid
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 Prophylaxis

• The rabies vaccine

– Intramuscularly on the day of exposure and then

on days 3, 7, 14, and 28

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 Prevention

• Ultimately the prevention of human rabies hinges on the

effective control of rabies in domestic and wild animals.

• Its control in domestic animals depends on the removal

of stray and unwanted animals and the vaccination of all
dogs and cats.

• A variety of attenuated vaccines for animal

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Summary

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Virology, 2023 113
 Filoviruses
• They are filamentous,
enveloped, -ssRNA
viruses.
• U-shaped, six-shaped
• The nucleocapsid is helical
• These agents cause severe
or fatal hemorrhagic fever
and are endemic in Africa.

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 Filoviruses

• In 1967 in the town of Marburg in Germany some laboratory

workers became ill with a haemorrhagic fever
• Had been in contact with blood, organs and cell cultures from
African green monkeys caught in Uganda.
• Seven of those affected died, and there were five cases of the
illness
• Investigations revealed that the monkeys had been infected with a
virus, never previously encountered, later named as Marburg virus

Virology, 2023 115

 Filoviruses

• In 1976 there were outbreaks of a similar disease in Africa

near the River Ebola in the Democratic Republic of Congo
(then Zaire) and in Sudan.

• A virus similar to Marburg virus was isolated from patients

and was named Ebola virus.

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Ebola virus and its spread

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 Pathogenesis

• The Ebola virus binds to the Niemann-Pick C1 (NPC1)

protein enters the cell , by G protein

• Replicate efficiently, producing large amounts of virus in

endothelial cells, monocytes, macrophage, DC, and other
cells.

• Elicits a cytokine storm of pro-inflammatory cytokines

• Similar to a super-antigen

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Pathogenesis cotn’d…

• Cytokine storm promoting sepsis-like

symptoms=>causes extensive tissue necrosis in
parenchymal cells of the liver, spleen, lymph nodes,
and lungs.
• Infection of endothelial cells => leading to vascular
injury and leakage.
• The widespread hemorrhage that occurs in affected patients causes edema,
hypovolemic shock, and disseminated intravascular coagulopathy (DIC)

• Ebola glycoproteins.
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Host immune responses to Ebola virus

Virology, 2023 120

 Epidemiology

• Rare cases of Marburg virus infection have been seen in

Zimbabwe and Kenya.
• Outbreaks of Ebola virus disease have occurred in the
Democratic Republic of Congo and Sudan.
• Since 1976, when the virus was discovered,
approximately 1850 cases and more than 1200 deaths
have occurred.

Virology, 2023 121

 Epidemiology cotn’d…

• In rural areas of central Africa, as much as 18% of the population

have antibody to this virus, subclinical infections do occur.
• These viruses may be endemic in bats or wild monkeys and can
be spread to humans and between humans.
• Contact with the animal reservoir or direct contact with infected
blood or secretions can spread the disease.
• These viruses have been transmitted by accidental injection and
through the use of contaminated syringes.

Virology, 2023 122

2014 Ebola Outbreak in West Africa

Virology, 2023 123

 Clinical Syndromes
• Marburg and Ebola viruses are the most severe causes of viral
hemorrhagic fevers
• The illness usually begins with flulike symptoms, such as
headache and myalgia.
• Nausea, vomiting, and diarrhea occur within a few days; a rash
also may develop.
• Subsequently, hemorrhage from multiple sites (especially the
gastrointestinal tract)
• Death occur in as many as 90% of patients with clinically
evident disease.
Virology, 2023 124
 Laboratory Diagnosis: Ebola

• All specimens from patients with a suspected filovirus

infection must be handled with extreme care to prevent
accidental infection.

• Handling of these viruses requires level 4 isolation

procedures that are not routinely available.

Virology, 2023 125

 Laboratory Diagnosis: Ebola

• Marburg virus may grow rapidly in tissue culture

(Verocells), but animal (e.g., guinea pig) inoculation may be
necessary to recover Ebola virus.
• Viral antigens by ELISA and RT-PCR

Virology, 2023 126

 Prevention, and Control: Fever
1. Isolate patient in single room with a private bathroom and
with the door to hallway closed

2. Implement standard, contact, and droplet precautions

3. Notify the hospital Infection Control Program and other

appropriate staff

4. Evaluate for any risk exposures for Ebola

5. IMMEDIATELY report to the health department

Virology, 2023 127

Togaviridae

Virology, 2023 128

 Togaviruses

• +ssRNA

• Enveloped,
icosahedral symmetry

• Important members
– Arboviruses

– Rubella virus

Virology, 2023 129

 Rubella virus

• Unlike the other togaviruses, rubella is a respiratory virus

• Rubella is one of the five classic childhood

exanthems

• Rubella, meaning “little red”

• First distinguished from measles and other

exanthems by German physicians; thus the common
name for the disease, German measles.

Virology, 2023 130

 Epidemiology of Rubella

• An endemic disease with worldwide distribution.

• Infection is initiated primarily through contact with

respiratory secretions.

• The virus is shed during the prodromal phase and up to a

week after the rash appears.

• Only moderately communicable,

 close living conditions are required for its spread.

Virology, 2023 131

 Epidemiology of Rubella

• Most cases are reported among

 Adolescents and young adults in military training camps,

 Colleges, and

 Summer camps.

• The greatest concern is that non-immune women of

childbearing age, congenital rubella.

Virology, 2023 132

 Infection and Disease

• Two forms of rubella can be distinguished:

1. Postnatal infection: develops in children or adults

2. Congenital (prenatal) infection: of the fetus is expressed

in the newborn as various types of birth defects.

Virology, 2023 133

 Postnatal Rubella
• Incubation period of 2 to 3 weeks,
• The rash of pink macules and
papules:
 First appears on the face and
progresses down the trunk and
toward the extremities,
 Advancing and resolving in about 3
days.
• Generally mild and produces lasting
immunity.
Virology, 2023 134
 Congenital (Prenatal) Infection

• Teratogenic - its transmission to a fetus can result in a serious

complication called congenital rubella
• The mother is able to transmit the virus even if she is
asymptomatic.
• The nature of the disorder is determined by the
– Tissue affected
– Stage of development disrupted.

• Since the vaccine era, CMV has replaced rubella as the most
common cause of congenital defects.
Teratogenic properties and is capable of crossing the placenta and infecting the fetus
where it stops cells from developing or destroys them
Virology, 2023 135
 Congenital (Prenatal) Infection

• First trimester is most likely to induce miscarriage or

multiple permanent defects in the newborn such as

Cardiac abnormalities
Ocular lesions
Deafness, and mental and physical retardation.
• Less drastic sequelae that usually resolve in time are
anemia, hepatitis, pneumonia, carditis, and bone
infection.
Virology, 2023 136
 Congenital (Prenatal) Infection

• An infant born with congenital rubella can

manifest a rash

Virology, 2023 137

 Diagnosis of Rubella

• Mimics other diseases and is often asymptomatic,

 Should not be diagnosed on clinical grounds alone.

• The confirmatory methods of choice are serological

testing and virus isolation systems.

• IgM tests can determine recent infection, and a rising titer

is a clear indicator of continuing rubella infection.

Virology, 2023 138

 Prevention of Rubella

• No specific therapy for rubella is available,

• Most control efforts are directed at maintaining herd

immunity with attenuated rubella virus vaccine.

• Testing of adult women is often recommended to

confirm prior infection and protective antibodies.

Virology, 2023 139

 Prevention of Rubella

• The current recommendation for non-pregnant, antibody-

negative women is immediate immunization.

• Sexually active women must utilize contraception for 3

months after the vaccine is administered.

• Antibody negative pregnant women should not be

vaccinated and must be monitored for rubella infection.

Virology, 2023 140

 Arboviruses

• Eastern and Western equine encephalitis

• Bird reservoir

• Mosquito vectors

• Symptoms include fever, encephalitis, rash

• Cell culture possible, but serology most

commonly used

Virology, 2023 141

Arboviruses

Virology, 2023 142

Flaviviridae

+ssRNA, Enveloped virus

Virology, 2023 143

Flaviviridae
Hepatitis C virus
Arboviruses

Virology, 2023 144

 Dengue fever

• +ssRNA, Enveloped virus

• Closely related, but anti-
genically distinct, virus
serotypes (DEN-1, DEN-2,
DEN-3, and DEN-4),
• Infection with one of these
serotypes provides immunity
to only that serotype for life

Virology, 2023 145

 Dengue fever

• Transmitted by
mosquitoes
• This disease used to be
called "break-bone" fever
=>causes severe joint and
muscle pain that feels like
bones are breaking.

Aedes aegypti mosquito

Virology, 2023 146

 Clinical Manifestations

• Any or few of the following events can occur.

– Fever,

– Severe head ache

– Muscle and joint pains

– Nausea, vomiting,

– Eye pain

Virology, 2023 147

 Dengue fever
• Dengue fever is also known as break-bone fever; the
symptoms and signs consist of high fever, headache,
rash, and back and bone pain that last 6 to 7 days.

• Dengue virus is a major worldwide problem, with up

to 100 million cases of dengue fever and 300,000
cases of dengue hemorrhagic fever (DHF) occurring
per year.
Virology, 2023 148
 Dengue Hemorrhagic Fever

• Common in children, passively acquired maternal

antibodies.
• In other ( Adults ) the presence of antibodies due to
previous infection with different serotype
• Important cause of morbidity and mortality in
Dengue
• Presence of existing Dengue antibody, associated
with fresh viral infection with new serotype
complexes and forms within few days of the second
dengue infection=>cause cytokine stormy=>DIC

Virology, 2023 149

 Clinical Syndromes

• DHF and dengue shock syndrome (DSS).

• Weakening and rupture of the vasculature, internal

bleeding, and loss of plasma, leading to shock
symptoms and internal bleeding.

Virology, 2023 150

 Diagnosis

• RT-PCR, is a highly sensitive tool in Diagnosis

• Serology, Viral protein specific IgM or IgG by ELISA

• Analysis of paired acute and convalescent sera to

show significant rise in antibody titer is the most
reliable evidence of an active dengue infection.

Virology, 2023 151

 Prevention

• Control of Mosquito breeding places.

• Anti mosquito measures
• Use of Insecticides.
• Screened windows and doors can reduce exposure to
vectors.

• No Vaccine available,
difficult in view of four
serotypes.

Virology, 2023 152

 Yellow fever

• Family: Flaviviridae
• Genus: Flavivirus
• An acute viral hemorrhagic disease Originated
in Central Africa
• 84 000–170 000 cases and up to 60 000
deaths
• Is transmitted by infected mosquitoes Aedes aegypti

Virology, 2023 153

 Yellow fever cotn’d…

• Yellow fever infections are characterized by severe systemic

disease, with degeneration of the liver, kidney, and heart, as well
as hemorrhage.
• Liver involvement causes the jaundice from which the disease
gets its name, but massive gastrointestinal hemorrhages (“black
vomit”) may also occur.
• The mortality rate associated with yellow fever during epidemics
is as high as 50%.

Virology, 2023 154

Yellow fever cotn’d…

• The incubation period is

3–6 days.
• Yellow eyes
• Headache
• Backache
• Vomiting
• Bleeding
• Death occurs on day 7–
10 of illness.
Virology, 2023 155
 Laboratory Diagnosis

• Detection and characterization can be performed by RT-PCR

testing of genomic RNA or viral mRNA in blood or other samples.

• After isolation, the viral RNA can also be distinguished by the

finding of RNA “fingerprints” of the genomic RNA.

• Monoclonal antibodies to the individual viruses have become a

useful tool for distinguishing the individual species and strains
of viruses

Virology, 2023 156

 Prevention, and Control

• No treatments exist for arbovirus diseases,

other than supportive care.

• The easiest means of preventing the spread of

any arbovirus is elimination of its vector and
breeding grounds.

• A live vaccine against yellow fever virus

Virology, 2023 157

 ZikaVirus

• +ssRNA
• Enveloped, Icosahedral.
• Contains envelope proteins
E and M.
• Family: Flaviviridae
• Genus: Flavivirus
• Species: Zika virus
• Reserviour : Aedes
mosquitoes
Virology, 2023 158
 Epidemiology
• First isolated in April 1950 =>monkey=>Zika Forest
of Uganda
• Since the 1950s has been known to occur within a
narrow equatorial belt from Africa to Asia.

• In 2014, the virus spread eastward across the Pacific

Ocean to South America, where the Zika outbreak has
reached pandemic levels.

Virology, 2023 159

 Symptoms

• Many infections are

asymptomatic
• Acute onset of fever
• Maculopapular rash
• Headache
• Joint pain
• Conjunctivitis (red eyes)
• Muscle pain

People usually don’t get sick enough to go to

the hospital, and they very rarely die of Zika.
 Microcephaly

• A neurological disorder in
which babies are born with
smaller than normal heads and
brains

In pregnant woman, the virus may cross the

placenta and infect the foetus’s neural
progenitor cells (NPC)=> creates fewer
neurons=>, leading to decreased brain
volume.
 Diagnostic testing for Zika virus

• Diagnosed by performing RNA nucleic acid testing

(NAT) on serum and urine, and possibly whole
blood, cerebral spinal fluid, or amniotic fluid 4

• Serology assays can also be used to detect Zika

virus-specific IgM

Virology, 2023 162

 Assessing pregnant women

• Possible exposure: during their current pregnancy

– Recent travel to or residence in an area with risk of Zika during

their pregnancy or periconceptional period ( 8 weeks before
conception).
– Sex without a condom with a partner who has traveled to or
lives in an area with risk of Zika.
Picornaviridae

Virology, 2023 164

Representatives of the Human Picornaviruses

Virology, 2023 165

Picornaviruses that infect humans

Virology, 2023 166

 Structure

• Virion is a naked, small(25

to 30 nm)
• Icosahedral capsid
• +ssRNA genome.
• VP1, VP2, and VP3 particles
are on the surface of the
capsid whereas the VP4
particle is inside the capsid.

Virology, 2023 167

 Unique Properties of Picornaviruses

• Resistant to
– pH 3 to pH 9

– Detergents

– mild sewage treatment

– heat

• Rhinoviruses are labile at acidic pH; optimum growth

temperature is 33° C.

Virology, 2023 168

 Disease Mechanisms of Picornaviruses

• Receptor, Intercellular adhesion molecule-1 (ICAM-1)

expressed on epithelial cells, fibroblasts, and endothelial
cells.

Rhinoviruses and several enterovirus

• Poliovirus binds to a different molecule (PVR/CD155)

• Enteroviruses enter via the oropharynx, intestinal mucosa, or

upper respiratory tract and infect the underlying lymphatic tissue

Virology, 2023 169

 Disease Mechanisms cotn’d….

• Rhinoviruses are restricted to the upper respiratory tract.

• In the absence of serum antibody, enterovirus spreads by

viremia to cells of a receptor-bearing target tissue.

• The infected target tissue determines the subsequent disease.

• Viral, rather than immune, pathologic effects are usually

responsible for causing disease.

Virology, 2023 170

Disease Mechanisms cotn’d….

Virology, 2023 171

 Transmission

• Fecal-oral route: poor hygiene,

dirty diapers (especially in day-
care settings)

• Ingestion via contaminated

food and water

• Contact with infected hands

and fomites

Virology, 2023 172

Poliovirus Infections

Virology, 2023 173

 What is polio disease?

• Polio (also called Poliomyelitis) is a highly infectious

disease caused by a virus
• The virus invades the nervous system and can cause
permanent paralysis
• Polio is spread through person-to-person contact and
can spread rapidly through a community
• However, one in 200 infections leads to permanent
paralysis (can’t move parts of the body) and even
death www.immune.org.nz
 Poliovirus Infections

The stages of infection and pathogenesis

a. The virus is ingested.

b. Local replication & intestinal replication.

c. Cross into certain nerve cells.

d. The intestine actively sheds viruses.

Virology, 2023 175

 How does poliovirus spread?
• Poliovirus infection is highly contagious
• Poliovirus is spread mostly by the fecal-oral route
– Primary mode of transmission – passage of the virus in stool to the
mouth of another child
– Can also be spread through saliva or droplets from a sneeze or
cough

Child excretes virus in Virus transferred to objects Virus transferred to Virus transferred ingested Next cycle of infection
stool and does not wash from hands another child’s hands
hands after using the
bathroom
 Types of polioviruses
• 3 Types of polioviruses
– Wild poliovirus (WPV) – 3 serotypes
• Type 1 – 359 cases in 2014 this is the only type of WPV in
circulation today)
• 85% of the cases of paralytic polio caused by type 1.

• Type 2 – eliminated in 1999

• Type 3 – last case reported in Nov. 2012 (more time is

needed to certify eradication)
 Poliovirus Infections

• May cause one of the following four outcomes in

unvaccinated people, depending on the progression of the
infection.

1. Asymptomatic illness

2. Abortive poliomyelitis, the minor illness

3. Non-paralytic poliomyelitis or aseptic meningitis

4. Paralytic polio, the major illness

Virology, 2023 178
 1. Asymptomatic illness

 Results if the viral infection is limited to the oropharynx

and the gut.

 At least 90% of poliovirus infections are asymptomatic.

Virology, 2023 179

 2. Abortive poliomyelitis, the minor illness

 Is a non-specific febrile illness occurring in

approximately 5% of infected people.

 Fever, headache, malaise, sore throat, and vomiting

occur in such persons within 3 to 4 days of exposure.

Virology, 2023 180

 3. Non-paralytic poliomyelitis or aseptic
meningitis

 Occurs in 1% to 2% of patients with poliovirus

infections.

 The virus progresses into the central nervous system

and the meninges

 Causes back pain and muscle spasms in addition to the

symptoms of the minor illness.

Virology, 2023 181

 4. Paralytic polio, the major illness

• Occurs in 0.1% to 2.0% of persons with poliovirus

infections and is the most severe outcome.

• It appears 3 to 4 days after the minor illness has subsided.

• The virus spreads from the blood to the cells of the

spinal cord and to the motor cortex of the brain.

• Asymmetric flaccid paralysis with no sensory loss low

muscle tone

Virology, 2023 182

Paralytic polio, flaccid paralysis

Virology, 2023 183

 Paralytic polio cotn’d…

• The degree of paralysis varies,

 May involve only a few muscle groups (e.g., one leg) or

 There may be complete flaccid paralysis of all four extremities.

• The paralysis may then progress over the first few days
and may result in complete recovery, residual paralysis,
or death.
Virology, 2023 184
 Poliovirus
Infections
Progression of
poliovirus infection.

• Infection may be
asymptomatic or may
progress to minor or
major disease.

Virology, 2023 185

 Bulbar poliomyelitis

• Bulbar (cranial) paralysis may involve a combination of

cranial nerves and even the medullary respiratory center.

• May involve the muscles of the pharynx, vocal cords,

and respiration

• May result in death in 75% of patients.

• More severe

Virology, 2023 186

 Post-polio syndrome

• Is a sequela of poliomyelitis that may occur much later

in life (30 to 40 years later) in 2% of paralytic
sydrome.

• Affected persons suffer a deterioration of the originally

affected muscles.

• Poliovirus is not present, but the syndrome is believed to

result from a loss of neurons in the initially affected
nerves. Virology, 2023 187
 Franklin roosevelt

• 32nd president
• Infected in 1921
• Premanently damaged from the
waist down
• Miss-diagnosis
• GBS ASSYMETRIC
• POLIOASSYMETRICAL
DAMAGE

Virology, 2023 188

 Laboratory diagnosis
• Polioviruses may be isolated from the patient’s pharynx
during the first few days of illness, from the feces for as long
as 30 days, but only rarely from CSF.

• The virus grows well in monkey kidney tissue culture.

• Use of specific antibody and antigen assays (ELISA)

• RT-PCR

Virology, 2023 189

 Polio prevention

• Vaccine

• Similar to smallpox, polio has been

targeted for elimination.

Virology, 2023 190

Prevention(PV)

Virology, 2023 191

 Comparison of OPV and IPV?
Oral polio vaccine (OPV)
• Live, attenuated (weakened) virus
• Administered by drops
• Highly successful in reducing transmission
in developing countries as part of
eradication strategy
• Inexpensive
• Easy to administer
• Provides humoral immunity and
mucosal/gut immunity
• Protects close contacts who are
unvaccinated
Inactivated polio vaccine (IPV)
• Killed virus
• Administered by injection
• Highly effective and safe
• Used commonly in developed countries
• More expensive than OPV
• Requires trained health workers
• Provides humoral immunity
• Carries no risk of VAPP or cVDPV
Both vaccines are needed
to fully eradicate polio!
 Polio – the world in 1988

>350,000 cases

>125 polio-endemic
countries

1988: World Health Assembly Resolution

 Polio - the world in 2008

423 cases

Endemic country
Re-infected country

Since 1988: >99% reduction in disease

Since 1988, polio has been eliminated in 122 countries

Virology, 2023 195

Coxsackie A Virus

Virology, 2023 196

 Coxsackie A Virus
Causes=Herpangina
 Fever, sore throat, pain on swallowing,
anorexia, and vomiting characterize this
disease.
 The classic finding is vesicular ulcerated
lesions around the soft palate and uvula
 Less typically, the lesions affect the hard
palate.
 The virus can be recovered from the lesions
or from feces.
 The disease is self-limited and requires
only symptomatic management. Virology, 2023 197
 Hand-foot-and-mouth disease

 Is a vesicular exanthem usually caused by Coxsackievirus

A16.

 The name is descriptive because the main features of this

infection consist of vesicular lesions on the hands, feet,
mouth, and tongue

 The patient is mildly febrile, and the illness subsides in a

few days

Virology, 2023 198

 Coxsackie A Virus

Hand-foot-and-mouth
disease caused by
Coxsackie A virus.

• Lesions initially
appear in the oral
cavity and then
develop within 1
day on the palms
and, as seen here,
on soles.
Virology, 2023 199
Coxsackie B virus

Virology, 2023 200

 Coxsackie B virus

• Pleurodynia (Bornholm disease),also

known as the devil’s grip
 is an acute illness in which patients have
a sudden onset of fever and unilateral
low thoracic, chest pain.
 Abdominal pain and even vomiting may
also occur, and muscles on the involved
side may be extremely tender.

Virology, 2023 201

 Coxsackie B virus cotn’d….

• Myocardial and pericardial infections

 Occur sporadically in older children and adults but are
most threatening in newborns.

 Neonates with these infections have febrile illnesses and

sudden and unexplained onset of heart failure.

 The mortality associated with the infection is high

Virology, 2023 202

Echovirus

Virology, 2023 203

 Echovirus
• Viral (aseptic) meningitis
• is an acute febrile illness accompanied by headache and signs
of meningeal irritation, including nuchal rigidity.

• Petechiae or a rash may occur in patients with enteroviral

meningitis.

• Recovery is usually uneventful, unless the illness is associated

with encephalitis (meningoencephalitis) or occurs in children
younger than 1 year.

Virology, 2023 204

 Laboratory Diagnosis

• Cerebrospinal fluid (CSF) from enterovirus aseptic

meningitis can be distinguished from bacterial
meningitis.

• The CSF lacks neutrophils, and the glucose level is

usually normal or slightly low.

• The CSF protein level is normal to slightly elevated.

• The CSF is rarely positive for the virus.

Virology, 2023 205

 Laboratory Diagnosis: Culture
• Coxsackieviruses and echoviruses can usually be isolated
from the throat and stool during infection and often from
CSF in patients with meningitis.

Virology, 2023 206

 Prevention and Control

• There are no vaccines for Coxsackieviruses or echoviruses.

• Transmission of these viruses can presumably be reduced by

improvements in hygiene and living conditions.

Virology, 2023 207

Rhinoviruses

Virology, 2023 208

 Rhinoviruses

• are the most important cause of the common cold and upper
respiratory tract infections.

• Such infections are self-limited, however, and do not cause

serious disease.

• More than 100 serotypes of rhinovirus have been identified.

• At least 80% of the rhinoviruses have a common receptor that is

also used by some of the Coxsackieviruses.

• This receptor has been identified as ICAM-1

Virology, 2023 209

 Pathogenesis
• Unlike the enteroviruses, rhinoviruses are unable to replicate
in the gastrointestinal tract

• The rhinoviruses are labile to acidic pH.

• Also, they grow best at 33°C, a feature that contributes to their

preference for the cooler environment of the nasal mucosa.

• Infection can be initiated by as little as one infectious viral

particle.

Virology, 2023 210

 Pathogenesis

• During the peak of illness, nasal secretions contain

concentrations of 500 to 1000 infectious virions per

milliliter.

• The virus enters through the nose, mouth, or eyes and

initiates infection of the URT, including the throat.

Virology, 2023 211

 Pathogenesis

• Most viral replication occurs in the nose, and the

onset and the severity of the symptoms correlate
with the time of viral shedding and the quantity
(titer) of virus shed.

• Infected cells release bradykinin and histamine,

which cause a “runny nose.”

Virology, 2023 212

 Clinical Syndromes

• Usually begins with sneezing, which is soon followed by

rhinorrhea (runny nose).

• Mild sore throat , along with headache and malaise

but usually without fever.

• The illness peaks in 3 to 4 days

• Cough and nasal symptoms may persist for 7 to 10 days

or longer.
Virology, 2023 213
Common cold symptoms

Virology, 2023 214

 Laboratory diagnosis

• The clinical syndrome of the common cold

is usually so Characteristic

• Laboratory diagnosis is unnecessary.

Virology, 2023 215

 Prevention, and control

• No antiviral drugs are available

• Hand washing and disinfection

of contaminated objects are the
best means of preventing viral
spread.

Virology, 2023 216

Noroviridae

Virology, 2023 217

 Noroviruses

• +ssRNA genome

• naked capsid

• Norwalk virion capsid is

icosahedral

Virology, 2023 218

 Transmission

• Viruses are resistant to environmental pressure:

detergents, drying, and acid.

• Viruses are transmitted by fecal-oral route in

contaminated water and food.

• Viruses cause outbreaks of gastroenteritis.

• Disease resolves after 48 hours, without serious

consequences.
Virology, 2023 219
 Pathogenesis

• The Norovirus strains that infect humans can only infect

humans.
• As few as 10 virions will initiate disease in humans.
• Damage to the intestinal brush border prevents proper
absorption of water and nutrients and causes a watery
diarrhea.
• Although no histologic changes occur in the gastric
mucosa, gastric emptying may be delayed, causing
vomiting.
Virology, 2023 220
 Pathogenesis cotn’d…

• Examination of jejunal biopsy specimens from human

volunteers infected with noroviruses revealed the existence of
blunted villi.

• Shedding of the virus may continue for 2 weeks after

symptoms have ceased.

• Immunity is generally short lived at best and may not be

protective.

• The large number of strains and high rate of mutation allows

reinfection despite antibodies from a previous exposure.
Virology, 2023 221
 Clinical Syndromes

• Symptoms similar to those caused by the rotaviruses.

• Acute onset of diarrhea, nausea, vomiting, and abdominal

cramps

• Bloody stools do not occur.

• The incubation period is usually 12 to 48 hours, and the illness

usually resolves within 1 to 3 days without problems but can last
up to 6 days.

Virology, 2023 222

 Laboratory Diagnosis

• The use of RT-PCR for detection of the Norovirus

genome in stool or emesis samples has enhanced the
speed and detection of the virus during outbreaks.

• ELISA tests have been developed to detect the virus, viral

antigen, and antibody to the virus.

Virology, 2023 223

 Prevention, and Control

• No specific treatment for infection

• Outbreaks may be minimized by handling food carefully and

by maintaining the purity of the water supply.

• Careful hand washing is also important.

• Norwalk virus is resistant to heat (60° C), pH 3, detergent,

and even the chlorine levels of drinking water.

• Contaminated surfaces can be cleaned with a 1 : 10 dilution

of household bleach.
Virology, 2023 224
Virology, 2023 225
Reoviridae

Virology, 2023 226

 Reoviridae
• Non-enveloped viruses
with double-layered
protein capsids
• Containing 11 segments
of the dsRNA genomes.
• Stable in detergents,
over wide pH and
temperature ranges, and
in airborne aerosols

Rotavirus are activated by mild proteolysis to

subviral particles, increasing their infectivity.
Virology, 2023 227
 Pathogenesis of Rotavirus

• The rotavirus can survive the acidic environment in a

buffered stomach or in a stomach after a meal and is
converted to the ISVP by proteases.

• Viral replication occurs after adsorption of the ISVP to

columnar epithelial cells covering the villi of the small
intestine.

• As many as 1010 viral particles per gram of stool may be

released during disease.

Virology, 2023 228

 Pathogenesis cotn’d…

• Similar to cholera, rotavirus infection prevents the absorption

of water,

o Causing a net secretion of water and loss of ions, which

together result in a watery diarrhea.

• The NSP4 protein of rotavirus acts in a toxin-like manner to

 Promote calcium ion influx into enterocytes,

 Release of neuronal activators, and a neuronal alteration in

water absorption.
Virology, 2023 229
 Pathogenesis cotn’d…

• The diarrhea also promotes spread and transmission of

the virus.

• Immunity to infection requires the presence of antibody,

primarily immunoglobulin A (IgA), in the lumen of the gut.

• Antibodies to the VP7 and VP4 neutralize the virus.

• Inoculation of even small amounts of virus causes

infection
Virology, 2023 230
 Clinical Syndromes

• Rotavirus is a major cause of gastroenteritis.

• The incubation period is estimated to be 48 hours.
• The major clinical findings in hospitalized patients are vomiting,
diarrhea, fever, and dehydration.
• Neither fecal leukocytes nor blood occurs in stool for this
form of diarrhea.
• Rotavirus gastroenteritis is a selflimited disease, and recovery is
generally complete and without sequelae.

Virology, 2023 231

 Laboratory Diagnosis

• Most patients have large quantities of virus in stool

• Direct detection of viral

• EM

• Antibody titer is necessary for the diagnosis of recent

infection or active disease.

Virology, 2023 232

 Prevention, and Control

• Two new safer rotavirus vaccines have since been developed

– RotaTeq consists of rotaviruses containing the VP4 or VP7

of five different human rotaviruses.

– The RotaRix vaccine is a single-strain attenuated human

rotavirus.

– The vaccines are administered as young as possible, at 2,

4, and 6 months of age.

Virology, 2023 233

Coronaviruses

Virology, 2023 234

 Coronaviruses
• Pathogens named after their strange crown-like spikes

• There are many types, most of which infect animals

and not humans

• Some evolved spreading to humans, becoming human

coronaviruses.

• Were first identified in the mid-1960s

Virology, 2023 235

 Coronaviruses structure
• +RNA genome.

• The glycoproteins appear as

club-shaped projections that
appear as a halo (corona)
around the virus.

• Endure the conditions in the

gastrointestinal tract and be
spread by the fecal-oral route.

Virology, 2023 236

Coronaviruses structure

Virology, 2023 237

Virology, 2023 238
 Coronaviruses

• Common HCoVs (lower pathogenicity):

– HCoV-229E (alpha)
– CoV-NL63 (alpha)
– HCoV-OC43 (beta)
– HCoV-HKU1 (beta)
• 21st Century HCoVs (higher pathogenicity):
– SARS-CoV (beta)
– MERS-CoV (beta)
– SARS-CoV-2(beta)

Virology, 2023 239

Animal origins of human coronaviruses

Virology, 2023 240

SARS-CoV & MERS-CoV Emergence

Virology, 2023 241

Virology, 2023 242
 1. SARS-CoV

• Emerged in 2002 in China's southern region.

• The disease has spread to more than two dozen
countries in Asia, Europe, South America, and
North America
• Infected 8,098 people and killed 774
• The fatality rate of SARS-CoV is about 10%.
Virology, 2023 243
 Symptoms

• High fever, chills, headache and body aches.

• Mild respiratory symptoms emerge, while diarrhea is
seen in 10 to 20 percent of patients.
• Dry, nonproductive cough that might be tied to low
oxygen levels.
• In about 10 to 20% of the cases, the patients may
need ICU and mechanical ventilation.
• Pneumonia, which can lead to severe and life-
threatening complications.

Virology, 2023 244

 2. MERS-CoV

• First emerged in Saudi Arabia in 2012.

• The symptoms of MERS include fever, cough,
and shortness of breath.
• People may develop pneumonia, while others
develop gastrointestinal symptoms, such as
diarrhea.
• The fatality rate of MERS is about 35%, which
is higher than the COVID-19

Virology, 2023 245

3. SARS-CoV-2

Virology, 2023 246

What is Novel Corona Virus (nCoV)

The ‘New or Novel corona

virus ,now called 2019-
nCoV,had not been
detected before the
outbreak reported in
Wuhan, China in
December 2019.

Virology, 2023 247

 2019 Novel Coronavirus

• First identified amid an outbreak of respiratory illness

cases in Wuhan City, Hubei Province, China.
• It was initially reported to the WHO on December 31,
2019.
• On January 30, 2020, the WHO declared the COVID-
19 outbreak a global health emergency.
• On March 11, 2020, the WHO declared COVID-19 a
global pandemic, its first such designation since
declaring H1N1 influenza a pandemic in 2009.

Virology, 2023 248

Virology, 2023 249
 Naming

• The WHO on 10th February 2020 proposed an official

name for the illness caused by new corona virus as
COVID-19
• The goal was to avoid the stigma to any of the
places, people or animals associated with the corona
virus.
– ‘CO’ stands for CORON
– ‘VI’ stands for VIRUS
– ‘D’ stands for DISE SE
 Naming
• On February 11, 2020, the Coronavirus Study Group
of the International Committee on Taxonomy of
Viruses issued a statement announcing an official
designation for the novel virus: severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2).

Virology, 2023 251

 Why New Viral Infections Emerging?
• New viral diseases
typically emerge because
of human activity that
brings people into
contact with wildlife,
such as:
– Road building,
– Hunting and
– Agriculture expansion

Virology, 2023 252

 The source of COVID-19

• COVID-19 -most cases

were handlers and
frequent visitors to the
Wuhan (Seafood
Wholesale Market)
• Two recent research
papers have pointed to
bats and snakes as the
possible culprits.
• Recently PANGOLINS !

Virology, 2023 253

Virology, 2023 254
How COVID-19 spreads?

• Air Droplets (Coughing,

Sneezing)
• Touching an object with
the virus on it , then
touching mouth, eyes or
nose before washing
hands
• Close personal contacts
(Touching, shaking hands)
• Rarely faecal

Virology, 2023 255

 Incubation period

• Time between infection & the onset of clinical

symptoms of period disease.

– WHO: 2-14 days

 Target cells

• Virus is transmitted by respiratory and fecal routes

• Infection is mediated by ACE2 receptor
– High expression
• Lung alveolar epithelial cells
• Intestinal enterocytes
– Low expression
• Blood vessels (virtually all organs)
• Pneumonia
– Cause of death is lung failure

Virology, 2023 257

 0

• Replication

Virology, 2023 258

Pathogenesis

Virology, 2023 259

Pathogenesis

Virology, 2023 260

 COVID-19 clinical sign

• Symptoms may include:

– Fever
– Fatigue
– Dry cough Children tend to have milder disease than
– Headache adults

– shortness of breath
– diarrhea and nausea/vomiting
• 80% of cases are mild
• 20% of cases requires hospitalization
 COVID-19 clinical sign

• Symptoms begin about 5-6 days after

exposure, but can range from 2-14 days
• Severe complications include pneumonia and
kidney failure
– ~3.4% reported CFR.
• Chance of death increases with age and presence of
underlying medical conditions
• Cases were decreasing in china but increases
in other countries
Mortality

Virology, 2023 263

 Antibody response to SARS-CoV-2

• Most COVID-19 patients who recover have antibodies to

SARSCoV-2 detectable in their blood

• Most COVID-19 patients develop antibodies about 1-3

weeks after symptoms appear.

• Patients who have had more severe disease appear to

have higher levels of neutralizing antibodies.

• Antibodies remain for several months >5 months

Virology, 2023 264

Neutralizing antibodies bind to viral proteins

Virology, 2023 265

 Re-infection of SARS-CoV-2

• Generally, a person who recovered from a viral

infection is protected against a new infection.

• It is not yet known how long protection will last after

a SARS-CoV-2 infection

• Several cases of repeat SARSCoV-2 infection have

been reported

Virology, 2023 266

 SARS-CoV-2 variants & re-infection

• Recently, several SARS-CoV-2 variants have

emerged that involve genetic mutations of the spike
protein
• Variants identified in
– South Africa
– Brazil
– Uk
• Studies are ongoing to determine if a new variant
may lead to more cases of re-infection

Virology, 2023 267

Virology, 2023 268
 Laboratory Diagnosis

• Specimen: blood, respiratory and stool samples

– RT-PCR

– Antigen test

– Antibody test

Virology, 2023 269

 1. PCR tests

• Gold standard for COVID-19 diagnostics

• Detects the presence of SARS-CoV-2 viral
nucleic acids, generally during acute phase of
infection
•
• Home collection, pooling, point-of-care, multi-
test

Virology, 2023 270

 PCR tests

• Result Interpretation:
• Positive: Active
infection with SARS-
CoV-2 (doesn’t rule out
co-infection)
• Negative: Likely not
infected when the
sample was collected
(snapshot in time)

Virology, 2023 271

 PCR tests
Limitations:
• Sample collection &
transport impact test
accuracy
• Individuals may still test
positive by PCR but not
be infectious
• Turnaround time ranges
(from 2 hr to multiple
days)
Virology, 2023
Benefits:
• Most sensitive and
specific
• Gold standard to
diagnose acute infection
• Can identify infection in
asymptomatic
individuals
• Can be used for
diagnostics, screening,
and surveillance
272
 2. Antigen tests

• Quicker, cheaper, but less sensitive

• Detects the presence of SARS-CoV-2 by
binding to viral surface proteins (antigens)
• Result Interpretation:
• Positive: Active infection with SARS-CoV-2,
person is presumed to be contagious
• Negative: Does not rule out infection, may be
considered presumptive & confirmed with a
molecular test

Virology, 2023 273

 Antigen tests
Benefits:
Limitations: • Rapid (~15min)
• No amplification step=far • High specificity
less sensitive (risk for false • May be useful for
negatives) screening in high-risk
• Best for symptomatic congregate settings
individuals early during • Positive result informs
infection (when viral load clinical decisions and/or
is highest) infection control measures

Virology, 2023 274

 3. Antibody tests
• Useful to assess exposure, not for diagnosis
• Detects the body’s immune response to SARS-CoV-2
(ie past infection, not active infection)
• Takes 2-3 weeks post-infection to develop antibodies
(IgM, IgG)
• Result Interpretation:
• Positive: Previous infection with SARS-CoV-2.
Does not indicate current infection.
• Negative: Probably has not been infected with
SARS-CoV-2
• or too early in infection to have detectable
antibodies
Virology, 2023 275
 Antibody tests
Limitations:
• Risk of false positives (cross- Benefits:
reactivity)–can be minimized • Determining population-
by using a test with very high level exposure,
specificity (>99.5%)
especially when some
• Should not be used to
diagnose active infection or are asymptomatic
determine return to • Determining who can
work/school donate blood/plasma as
• Unknown how long possible treatment for
protective antibodies last severely ill
(months?)

Virology, 2023 276

 Prevention, and Control

• Control of the respiratory transmission of the

common cold form of coronavirus would be
difficult

• Strict quarantine (isolation) of individuals

infected with SARS-CoV

• Screening for fever in travelers

• No specific antiviral therapy is available.

Virology, 2023 277
How to protect ourselves & others

Virology, 2023 278

Vaccine Platform

Virology, 2023 279

 Covid-19 vaccine

• Three vaccines have received FDA Emergency

Use Authorizations (EUAs) :
– Pfizer/BioNTech=>mRNA

– AstraZeneca=>VECTOR

• A 2-dose schedule.

• Duration of protection is not yet known.

Virology, 2023 280

 Pifzer BioNtech

 a messenger ribonucleic acid (mRNA) vaccine.

 It contains the genetic sequence (mRNA) for the spike

protein
 Wrapped in a lipid envelope (referred to as a
nanoparticle) to enable it to be transported into the cells
in the body.

 When injected, the mRNA is taken up by the host’s

cells which translate the genetic information and
produce the spike proteins.

Virology, 2023 281

 Covid-19 vaccine

• Principle

– mRNA vaccines carry genetic

material that teaches cells how

to make a harmless piece of

“spike protein,” which is

found on the surface of the

SARS-CoV-2 virus.

Virology, 2023 282

 AstraZeneca

 A viral vector vaccine which uses a weakened

adenovirus as a carrier to deliver the SARS-CoV-2
antigen.

 The genes that encode for the spike protein on the

SARS-CoV-2 virus have been inserted into the
adenovirus's genetic code to make the vaccine.

Virology, 2023 283

 Can I get COVID-19 from the COVID-19 vaccines?

No. The vaccines do not contain the live virus that causes COVID-19. This means that you
can’t catch COVID-19 from the vaccine.

Virology, 2023 284

 RNA Vaccines have 2parts

RNA Coding for Spike Protein

Lipid Nanoparticles
 How do RNA Vaccines Work against SARS-
CoV-2?

Host cell Ribosome

nucleus

Virology, 2023 286

Retroviridae

Virology, 2023 287

 Retroviruses
• These are RNA viruses that belong to family
Retroviridae (Re = Reverse, tr = transcriptase).

• Members of this family possess an RNA genome and

the characteristic biochemical feature is the presence
of RNA dependent DNA polymerase (reverse
transcriptase) within the virus.

Virology, 2023 288

Classification

Virology, 2023 289

 Types of HIV Virus

• HIV 1
– Most common in sub-Saharan Africa and
throughout the world
– Groups M, N, and O
– Pandemic dominated by Group M
 Group M comprised of subtypes A - J

• HIV 2
– Most often found in West Central Africa, parts of
Europe and India

290 Virology, 2023

 HIV

• An RNA retrovirus

• Contains:
– 2 copies of RNA
– Enzymes:
• Reverse Transcriptase
• Integrase
• Protease
– Two major envelope proteins:
• gp120
• gp41
291 Virology, 2023
HIV STRUCTURE

• HIV is composed
of three main
layers:

• Envelope

• Viral Matrix

• Core

Virology, 2023 292

 Structure cotn’d…

• Genome is not infectious

• Three major genes that encode poly proteins:

– Gag (group-specific antigen, capsid, matrix, and nucleic acid–
binding proteins),

– Pol (polymerase, protease, and integrase), and

– Env (envelope, glycoproteins).

Virology, 2023 293

Structure cotn’d…

• The gp120 of HIV is

extensively glycosylated,
 Its antigenicity can drift

 These factors impede

immune clearance of the
virus.

Virology, 2023 294

 HIV Replication

• Primary receptor is CD4 protein

• CCR5 the co-receptor used upon initial infection of an
individual
 expressed on myeloid, peripheral, and subsets of helper T
cells (macrophages, [M]-tropic)

• Later, the env gene mutates, gp120 binds to a

different chemokine receptor (CXCR4)
Expressed primarily on T cells (T-tropic)
Virology, 2023 295
Target cell binding of HIV

Virology, 2023 296

 HIV cellular targets

• Th cells
• APCs
• Brain cell
• Intestinal epithelium
Virology, 2023 297
 Overview of HIV life cycle

HIV life cycle:

1. Binding and Fusion
2. Entry
3. Reverse transcription
4. Integration
5. Viral RNA and protein expression
6. Assembly and budding
7. Maturation

HIV target cells:

CD4T cells,
Macrohpages,
Dendritic cells
Virology, 2023 298
HIV Infection

Virology, 2023 299

 Pathogenesis

• HIV primarily infects CD4 T cells and cells of the myeloid

lineage

 Monocytes, macrophages, alveolar macrophages of the

lung, DCs, and microglial cells of the brain.

• Virus causes lytic infection of permissive and induces

apoptosis of non-permissive CD4 T cells.

• Virus causes persistent low-level productive and latent

infection of myeloid lineage cells and memory T cells.

Virology, 2023 300

 HIV pathogenesis cotn’d….

• Virus causes syncytia formation, with cells expressing

large amounts of CD4 antigen (T cells); subsequent
lysis of the cells occurs.

• Virus alters T-cell and macrophage cell function.

• Virus reduces CD4 T-cell numbers

Virology, 2023 301

Pathogenesis of HIV

Virology, 2023 302

 HIV cellular targets

• CD4 T cells have a critical role in activating and

regulating CMI, especially toward intracellular
pathogens.

• HIV–induced loss of CD4 T cells results in loss of the

functions

Virology, 2023 303

CD4 T cells have a critical role

Virology, 2023 304

Virulence factors of HIV

• Spikes that mediate attachment to host cells,

• Reverse transcriptase

• Rapid mutation

• Formation of syncytia

Virology, 2023 305

 HIV Transmission

Infected body fluids transmit HIV via

– Sexual contact (without condom)

– Breast milk

– Transplacental infection of fetus

– Blood-contaminated needles

– Organ transplants

– Artificial insemination

– Blood transfusion
Virology, 2023 306
HIV Transmission
Anal vs vaginal ?
 People at Risk
• Intravenous drug abusers,

• Sexually active people with many partners

(homosexual and heterosexual)

• Prostitutes

• Newborns of HIV-positive mothers

• Sexual partners of infected individuals

• Blood and organ transplant recipients

Virology, 2023 309
Epidemiology of HIV

Virology, 2023 310

Prevalence of HIV, 2017

Virology, 2023 311

 Incubation period
• Few months to 10 years or even more
• 75% of people infected with HIV develop AIDS at
the end of 10 years
• Severity of illness determined by:
– amount of virus in the blood (viral load) and
– the degree of immune suppression (decreasing CD4
count)
• Higher the viral load, sooner immune suppression
occurs

Virology, 2023 312

 Window period

• Time between potential exposure to HIV infection and

appearance of Antibodies in blood: 4-12 weeks

• Sero-conversion:
Development of evidence of antibody response to a
disease

• Viral Load:

• The amount of HIV in the blood.

Virology, 2023 313

 Clinical Syndromes

• In the late 1970s and early 1980s, an unusual number of

young, the initial “4H club” of risk groups (homosexual men,
Haitians, heroin addicts, and hemophiliacs in the USA.

were noted to be dying of normally benign

opportunistic infections.
 Their symptoms defined a new disease, the acquired
immunodeficiency syndrome (AIDS).

Virology, 2023 314

 Clinical syndromes cotn’d…
• HIV disease progresses from an asymptomatic nonspecific
disease to profound immunosuppression, referred to as
AIDS
• The initial symptoms following HIV infection (acute phase,
2 to 4 weeks after infection)

• Followed by a period of asymptomatic infection or a

persistent generalized lymphadenopathy that may last for
several years=> the virus is replicating in the lymph nodes
Virology, 2023 315
Clinical syndromes cotn’d…

• Early infection:
• More common to develop a brief flu-like illness
two to Four weeks after becoming infected.
• Signs and symptoms may include:
– Fever
– Headache
– Sore throat
– Swollen lymph glands
– Rash
Virology, 2023 316
Clinical syndromes cotn’d…

• Later infection:
• May remain symptom-free for eight or nine years or
more
• You may develop mild infections or chronic symptoms
• Such as:
– Swollen lymph nodes — often one of the first signs of HIV
infection
– Diarrhea
– Weight loss
– Fever
– Cough

Virology, 2023 317

 Latest phase of infection:(AIDS) :
• AIDS criteria:
1. Person positive for the virus

2. They fulfill one of these additional criteria:

 They have a CD4 count <200 cells/μl

 Their CD4 cells account for fewer than 14% of all

lymphocytes.

 They experience one or more of a CDC-provided list of

AIDS defining illnesses (ADIs)

Virology, 2023 318

 Full-blown AIDS occurs

• When the CD4 T-cell <200/µl(oftentimes to 50/µl or

undetectable)

• Virus load is greater than 75,000 copies/ml

• Involves the onset of more significant diseases,

including HIV wasting syndrome (weight loss and
diarrhea for more than 1 month) and

• Opportunistic infections, malignancies, and dementia

Virology, 2023 319
The Progression of HIV Infection

Foundation
Virology, 2023 Fig19.16 320
 Mechanisms of CD4 depletion cotn’d…

•When the CD4 count falls below 200, patients

develop opportunistic infections and others.

•The median survival after the CD4 count has

fallen to <200 is 3.7 years, if untreated.

321 Virology, 2023

 AIDS-Defining
Illnesses

• Kaposi sarcoma

Kaposi sarcoma
lesions on the back
Virology, 2023 322
Indicator diseases of AIDS

Virology, 2023 323

Exposed, but not infected
 CCR5 mutation Survival with HIV Infection
 Effective CTLs

Long-term nonprogressors
 Mechanism not known

Virology, 2023 324

 Laboratory Diagnosis of HIV

• Tests for HIV infection are performed for one of 4 reasons:

1. To identify those with the infection so that antiviral drug therapy

can be initiated,

2. To identify carriers who may transmit infection to others

(specifically blood or organ donors, pregnant women, and sex
partners),

3. To follow the course of disease and confirm the diagnosis of

AIDS, or

4. To evaluate the efficacy of treatment

Virology, 2023 325
Virology, 2023 326
 Serology
• Serologic tests cannot identify recently infected people.

• HIV antibody may develop slowly, taking 4 to 8 weeks in

most patients;

However, it may take 6 months or more in as many

as 5% of those infected

Rapid Ab test

ELISA =>Ag and Ab

Virology, 2023 327

 HIV p24 Antigen

• Core protein of the virus

• EIA detects p24 antigen before antibody can be detected

 Detected 2 to 3 weeks after HIV infection

 Detected about 6 days before antibody tests become reactive

• Used for:
– Diagnosis of pediatric HIV-1 infections

– Blood bank safety (high incidence countries)

Virology, 2023 328

 Rapid screening tests

• Rapid screening tests

are available that detect
specific antibody in
blood or oral fluid from
a swab of the gums

Qualitative assay to detect HIV antibodies

Virology, 2023 329

 Western blot assay
• Demonstrates the
presence of antibody
to the viral antigens
(p24 or p31) and
glycoproteins (gp41
and gp120/160).

Virology, 2023 330

 Window Period

• Time from initial infection with HIV until antibodies

are detected by a single test

• Usually 3-8 weeks before antibodies are detected

• May test false-negative for HIV antibodies during this

time period

• Can still pass the virus to others during this period

331 Virology, 2023

Evolution of Antibodies

Virology, 2023 332

We can’t close the window

Virology, 2023 333

 Diagnosis of HIV Genomics

• Newer methods for detection and quantitation of HIV

genomes in blood

• Determination of the viral load (amount of genome in

blood)

• is an excellent indicator of the course of disease and

efficacy of therapy.

Virology, 2023 334

 Viral load

• Quantitative molecular assay measures amount of

HIV in blood products

• Used to:
– Predict disease progression

– Assist with deciding when to initiate anti-retroviral therapy

– Monitors response to anti-retrovirals

Virology, 2023 335

Common diagnostic methods

Virology, 2023 336

 Immunologic Studies

• The status of an HIV infection can be inferred from an

analysis of the T-cell subsets=>Disease progression.
• Severity of illness is determined by amount of virus in the
body (increasing viral load) and the degree of immune
suppression (decreasing CD4+ counts).

• As the CD4 count declines, the immune function

decreases.

337 Virology, 2023

 CD4 counts

• Used for:
– Determining clinical
prognosis
– Assessing criteria for
antiretroviral therapy
– Monitoring therapy

Virology, 2023 338

 Treatment

• Therapy should be initiated:

– For any individual positive for HIV

– For post-exposure prophylaxis (e.g., needle stick) if

HIV is detected in the individual.

Virology, 2023 339

 HAART
• Anti-HIV therapy is currently given as a cocktail of several antiviral drugs
termed highly active antiretroviral treatment (HAART)

• Advantages
 has less potential to select for resistance

 reduce blood levels of virus to nearly zero

 reduce morbidity and mortality in many patients with advanced AIDS.

 minimize the drug side effects,

 ease the pill-taking regimen, and

 allow the patient to return to nearly normal health and lifestyle.

Virology, 2023 340

Mechanisms of action of anti-HIV drugs

Virology, 2023 341

 Treatment

• The primary drawbacks to anti-HIV drugs are

High cost,

Toxic side effects,

Drug failure due to patient noncompliance, and

An inability to completely eradicate the virus.

Virology, 2023 342

 Prevention and Control

• Blood, Blood Product, and Organ Screening

• Infection Control

• Approaches to Prophylaxis

• Condoms and sterile needles!

• Health care workers use Universal Precautions:

– Wear gloves, gowns, masks, and goggles

– Do not recap needles

Virology, 2023 343
 Vaccine
• Difficulties due to
– Mutations
– Geographical clades
– Antibody-binding sites “hidden”
– Infected cells not susceptible to CTLs
– Proviruses
– Latent viruses

Virology, 2023 344

Summary

Virology, 2023 345