MEDICAL

MICROBIOLOGY II

DR. KELI, MBChB.

 Virology
Scope: description, classification, replication, transmission, role of
laboratory in virology, selected viruses of medical importance: Respiratory
viruses; Influenza, Rota, Measles, Mumps, HIV, Hepatitis, Herpes Simplex,
Varicella, Polio,, Yellow Fever, Rabies, Dengue Virus, Ebola.
Viruses
• Viruses are particles/ micro-organisms that have a simple structure composed of an
internal core containing either RNA or DNA (but not both) covered by a protective
protein coat.
• Some viruses have an outer lipoprotein membrane, called an envelope, external to
the coat.
• The nucleic acid core is packed within protein coat (capsid) which protects it during
transmission between host cells.
• Virion – is a complete virus particle
• Unclear whether viruses are living or not, hence are referred to as active and
inactive
• Viruses lack the metabolic machinery for isolation, multiplication and must invade a
host cell in order to reproduce.
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Viruses cont’d
• Viruses that infect bacteria are referred to as bacteriophages
• Viroids —small, single-stranded, covalently closed circular RNA molecules
existing as highly base-paired rod-like structures; they do not possess
capsids. Cause a number of transmissible plant diseases.
• Prions – abnormal pathogenic agents that are transmissible and able to
induce abnormal folding of specific normal cellular proteins.
• Are proteinaceous and infectious in nature. The cellular form of the prion
protein (PrPc) is encoded by the host's chromosomal DNA causing
neurodegenerative disorders.
• Prion diseases of importance:- Kuru, Creutzfeldt-Jakob disease (CJD),
Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia
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Viral capsid
• The capsid of the virus have various shapes.
• Polyhedral -Many sided
• Helical(coil)
• Bullet shaped.
• Spherical
• Viral nucleocapsids have two major forms of symmetry:
(1) icosahedral, in which the capsomers are arranged in 20 triangles that
form a symmetric figure (an icosahedron) with the approximate outline of a
sphere and
(2) helical, in which the capsomers are arranged in a hollow coil that
appears rod-shaped. The helix can be either rigid or flexible.
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Viral proteins
• Viral proteins serve several important functions.
• The surface proteins of the virus, whether they are the capsid proteins or the envelope
glycoproteins, are the principal antigens.
• They are also the determinants of type specificity (often called the serotype). E.g poliovirus types
1, 2, and 3 are distinguished by the antigenicity of their capsid proteins.
• The outer capsid proteins protect the genetic material and mediate the attachment of the virus to
specific receptors on the host cell surface.
• This interaction of the viral proteins with the cell receptor is the major determinant of species and
organ specificity.
• Outer viral proteins are also important antigens that induce neutralizing antibody and activate
cytotoxic T cells to kill virus-infected cells.
• These outer viral proteins not only induce antibodies but are also the target of antibodies, i.e.,
antibodies bind to these viral proteins and prevent ("neutralize") the virus from entering the cell
and replicating
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Viral proteins cont’d
• Some viruses produce proteins that act as "superantigens“ e.g.
Epstein-Barr virus and Cytomegalovirus, and the Retrovirus mouse
mammary tumor virus.
• Tegument, which is located between the nucleocapsid and the
envelope is a regulatory protein.
• These regulatory proteins include transcription and translation factors
that control either viral or cellular processes.
• Members of the herpesvirus family, such as herpes simplex virus and
cytomegalovirus, have a prominent, well characterized tegument

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General Properties Of Viruses
1. They are obligate intra-cellular parasites that reproduce within a living cell.
2. They are unicellular organisms (organisms without cell wall. Other are Chlamydia
and Rickettsiae)
3. They multiply within a cell by means of replication; not binaryfission like
bacteria.
4. They contain only one type of nucleic acid, which are DNA or RNA but not both
DNA and RNA. The genetic material can exist in many different forms
1. It can be double-stranded DNA or RNA.
2. It can be single-stranded DNA or RNA
5. Viruses infect animals, insects, bacteria, fungi, plants, humanbeings and
protozoa etc.
6. They are sensitive to interferons(anti-retro-viral drugs) but resistant to antibiotic.
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General Properties Of Viruses cont’d
7. They lack enzymes necessary for protein and nucleic acid synthesis and
other structures necessary for reproduction but depend on or upon
synthesized foods from the host cell.
8. They are either oval, round shaped or complex.
9. They cannot grow on ordinary laboratory cultures, embryonated eggs
and susceptible animals.
10. They are extremely small ranging in size (20-400nm in diameter)
11. Some viruses have an outer lipo-protein membrane called an Envelope.
12. Viruses do not have a nucleus, cytoplasm, mitochondria or ribosomes.

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DIFFERENCES BETWEEN BACTERIA
AND VIRUSES
Bacteria
• Have cell wall
• Large in size
• Contain RNA and DNA molecules
• Multiply by binary fusion
• Grow in inanimate culture media
• Have ribosomes.
• Are sensitive to antibiotics.
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Viruses
• Have envelope/ capsid.
• Small in size.
• Contain either RNA or DNA
molecules but not both
• Replicate inside organism and animal
• Cannot survive in inanimate culture
media
• Have no ribosome
• Not sensitive to antibiotics.
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Classification
• Viruses are classified into two major groups depending on the type of
nucleic acid material they posses.
• Those viruses that contain Ribo Nucleic acid (RNA) and those viruses that
contain Deoxy-Ribo Nucleic Acid (DNA).
• NB: Can also be classified according to:
• Virion morphology; size, shape, type of symmetry, presence or absence of
peplomers (spikes) etc.
• Virus protein properties, including number, size, and functional activities of
structural and nonstructural proteins,
• Antigenic properties.
• Biologic properties, including natural host range, mode of transmission, vector
relationships, pathogenicity, tissue tropisms, and pathology.
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Size/shapes of viruses

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Classification of medically important viruses

DNA VIRUSES RNA VIRUSES

• Parvovirus • Picornaviruses
• Caliciviruses
• Polyomaviruses • Reoviruses

• Papillomaviruses • Flaviviruses
• Togaviruses
• Adenoviruses • Retroviruses

• Hepadnaviruses • Orthomyxoviruses
• Paramyxoviruses
• Herpesviruses • Rhabdoviruses

• Poxviruses • Filoviruses
• Coronaviruses

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• Arenaviruses
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Modes of transmission
• Direct contact e.g. through kissing or sexual intercourse – transmission of infections like
Herpes virus. Neonates are occasionally infected at birth. E.g. HIV, Herpes simplex, Hepatitis B-
viruses
• Mechanical transmission by arthropods – Arboviruses e.g. Yellow fever, chikungunya, dengue,
Zika etc.
• Through bite - Rabies virus, excreted in saliva is transmitted by bites of rabid animals.
• The fecal-oral route - Poliomyelitis virus, Hepatitis A
• Airborne droplets - Influenza viruses, Measles viruses and Mumps virus.
• Transmission thr’ transfusion, inoculation or transplantation - Surgical instruments or
needles can be used as carriers of Hepatitis B virus
• Infection through contact with animals - Lassa fever virus( in the family: Arenaviridae) from
rodent excreta
• Direct transfer of viruses from one person to another e.g. Ebola
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Viral Pathogenesis
• This is the process by which viruses produce disease in the host.

• The pathogenic process of viral disease includes

1. Implantation of virus at the portal of entry,
2. Local replication,
3. Spread to target organs (disease sites), and
4. Spread to sites of shedding of virus into the environment.

• The consequences of viral infections depend on the interplay between

a number of viral and host factors.
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Viral pathogenesis cont’d
• The ability of a virus to cause degenerative changes in cells or cell
death is called cytopathogenicity.
• Viral strains that kill target cells and cause disease are called virulent
viruses.
• Other strains that have mutated and lost their ability to cause
cytopathic effects (CPE) and disease are termed as avirulent or
attenuated strains.
• Some attenuated strains can be used as live vaccines. Examples of live
attenuated vaccines are MMR (measles, mumps, rubella).

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Factors in Viral Pathogenesis
• Effects of viral infection on cells (Cellular Pathogenesis)
• Entry into the Host
• Course of Infection (Primary Replication, Systemic Spread, Secondary Replication)
• Cell/Tissue Tropism
• Cell/Tissue Damage

• Host Immune Response

• Virus Clearance or Persistence

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Viral Entry
• Skin - Most viruses which infect via the skin require a breach in the physical integrity of
this effective barrier, e.g. cuts or abrasions. Many viruses employ vectors, e.g. ticks,
mosquitos or vampire bats to breach the barrier.
• Conjunctiva and other mucous membranes - rather exposed site and relatively
unprotected
• Respiratory tract - In contrast to skin, the respiratory tract and all other mucosal surfaces
possess sophisticated immune defense mechanisms, as well as non-specific inhibitory
mechanisms (ciliated epithelium, mucus secretion, lower temperature) which viruses
must overcome.
• Gastrointestinal tract - a hostile environment; gastric acid, bile salts, etc. Viruses that
spread by the GI tract must be adapted to this hostile environment.
• Genitourinary tract - relatively less hostile than the above, but less frequently exposed to
extraneous viruses (?)
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Viral pathogenesis cont’d
• The ability of virus to cause disease can be viewed in two levels:-
1.Changes that occur within individual cell
2.Process that takes place in infected patient

• Cells can respond to viral infections in 3 ways:

1. No apparent change,
2. Death (lysis/inhibit protein synthesis),
3. Immuno-pathological mxns and
4. Transformation.

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Cellular Pathogenesis
• Direct cell damage and death from viral infection may result from:
• Lysis.
• diversion of the cell's energy
• shutoff of cell macromolecular synthesis
• competition of viral mRNA for cellular ribosomes
• competition of viral promoters and transcriptional enhancers for cellular transcriptional
factors such as RNA polymerases, and inhibition of the interferon defense mechanisms.
• Indirect cell damage can result from
• integration of the viral genome
• induction of mutations in the host genome
• inflammation
• host immune response.

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Immune Pathological Response
• Enhanced viral injury could be due to one or a mixture of the following
mechanisms;-
• Increased secondary response to T cells e.g. HBV
• Specific ADCC or complement mediated cell lysis
• Binding of un-neutralized virus-Ab complexes to cell surface Fc receptors, and
thus increasing the number of cells infected e.g. Dengue hemorrhagic fever,
HIV.
• Immune complex deposition in organs such as the skin, brain or kidney e.g.
rash of rubella and measles.

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Course of Viral Infection
• Local replication/disease.
• Primary Replication
• The place of primary replication is where the virus replicates after gaining initial entry into
the host.
• This frequently determines whether the infection will be localized at the site of entry or
spread to become a systemic infection.
• Systemic Spread
• Apart from direct cell-to-cell contact, the virus may spread via the blood stream and via
nerves the CNS.
• Secondary Replication
• Secondary replication takes place at susceptible organs/tissues following systemic spread.

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Cell Tropism
Viral affinity for specific body tissues (tropism) is determined by
• Cell receptors for virus.
• Cell transcription factors that recognize viral promoters and enhancer
sequences.
• Ability of the cell to support virus replication.
• Physical barriers.
• Local temperature, pH, and oxygen tension, enzymes and non-specific
factors in body secretions.
• Digestive enzymes and bile in the gastrointestinal tract that may
inactivate some viruses.
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Examples of cell tropism
• Polioviruses selectively infect and destroy certain nerve cells, which have a higher
concentration of surface receptors for polioviruses than do virus-resistant cells.
• Rhinoviruses multiply exclusively in the upper respiratory tract because they are
adapted to multiply best at low temperature and pH and high oxygen tension.
• Enteroviruses can multiply in the intestine, partly because they resist inactivation
by digestive enzymes, bile, and acid.
• Rabies virus uses the acetylcholine receptor present on neurons as a receptor, and
hepatitis B virus binds to polymerized albumin receptors found on liver cells.
• Similarly, Epstein-Barr virus uses complement CD21 receptors on B lymphocytes,
and human immunodeficiency virus uses the CD4 molecules present on T
lymphocytes as specific receptors.

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Outcome of Viral Infection
(1) Abortive infection, in which no progeny virus particles are produced, but the
cell may die because early viral functions can occur;
(2) Lytic infection, in which active virus production is followed by cell death; and
(3) Persistent infection, in which small numbers of virus particles are produced
with little or no CPE.
Persistent infections include
• latent infection, in which viral genetic material remains in host cell without production
of virus and may be activated at a later time to produce virus and/or transform the host
cell;
• chronic infection, which involves low level of virus production with little or no CPE; and
• viral transformation, in which viral infection or viral gene product induces unregulated
cellular growth, and cells form tumors in the host
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Outcome of Viral Infection cont’d
• Acute Infection
• Recovery with no residue effects
• Recovery with residue effects e.g. acute viral encephalitis leading to neurological sequelae.
• Death
• Proceed to chronic infection
• Chronic Infection
• Silent subclinical infection for life e.g. CMV, EBV
• A long silent period before disease e.g. HIV, SSPE, PML
• Reactivation to cause acute disease e.g. herpes and shingles.
• Chronic disease with relapses and exacerbations e.g. HBV, HCV.
• Cancers e.g. EBV, HTLV-1, HPV, HBV, HCV, HHV-8

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Viral Clearance or Persistence
• The majority of viral infections are cleared but certain viruses may cause
persistent infections. There are 2 types of chronic persistent infections.
• True Latency - the virus remains completely latent following primary infection
e.g. HSV, VZV. Its genome may be integrated into the cellular genome or exists as
episomes.
• Persistence - the virus replicates continuously in the body at a very low level e.g.
HIV, HBV, CMV, EBV.

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Mechanisms of Viral Persistence
• Antigenic variation
• Immune tolerance, causing a reduced response to an antigen, may be due to genetic
factors, pre-natal infection, molecular mimicry
• Restricted gene expression
• Down-regulation of MHC class I expression, resulting in lack of recognition of infected
cells e.g. Adenoviruses
• Down-regulation of accessory molecules involved in immune recognition e.g. LFA-3 and
ICAM-1 by EBV.
• Infection of immuno-priviliged sites within the body e.g. HSV in sensory ganglia in the CNS
• Direct infection of the cells of the immune system itself e.g. Herpes viruses, retroviruses
(HIV) - often resulting in immunosuppression.

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REPRODUCTION
• Viruses are not complete cells therefore cannot reproduce by themselves.
• They attach to the permissive receptor of the host cell membrane and inject
RNA or DNA which then takes control of the living cell.
• Viral genetic material is injected from the capsid to the recipient cell through
its tail.
• The viral particle does the following-
• Alter protein synthesis.
• Alter the gene of the host.
• Causes chromosomal changes.
• The cell then synthesizes new viral protein and nucleic acid, the process
continues until the cell raptures releasing new infective virions.
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 Virus replication cycle

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Viral Genetics
• Viruses generally use two mechanisms—mutation and recombination
—by which viral genomes change during infection.
• There are virologic, immunologic, and clinical consequences of some
of these changes
• Both mechanisms are responsible for allowing the virus to escape
preexisting immunity requiring the need for updating strains for
annual influenza vaccination and causing persistence viral infection
such as HIV.

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Role of laboratory in virology
There are five approaches to the diagnosis of viral diseases by the use
of clinical specimens:
(1)identification of the virus in cell culture
(2)microscopic identification directly in the specimen
(3)serologic procedures to detect a rise in antibody titer or the
presence of IgM antibody
(4)detection of viral antigens in blood or body fluids
(5)detection of viral nucleic acids in blood or the patient's cells

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Microscopic Identification
• Viruses can be detected and identified by direct microscopic
examination of clinical specimens such as biopsy material or skin
lesions.
• Three different procedures can be used.
(1) Light microscopy can reveal characteristic inclusion bodies or multinucleated
giant cells. The Tzanck smear, which shows herpesvirus-induced multinucleated
giant cells in vesicular skin lesions, is a good example.
(2) UV microscopy is used for fluorescent-antibody staining of the virus in
infected cells.
(3) Electron microscopy detects virus particles, which can be characterized by
their size and morphology

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Quantitation of Viruses
• Hemagglutination Assay - can be used to estimate the titer of virus particles in
a virus-containing sample. Eg influenza viruses,
• Plaque Assay is a method for determining the titer of infectious virions in a
virus preparation or lysate
• Immunologic Assay - Viral antigen can be quantified by using antigen–
antibody specificity, as measured by enzyme immunoassay (EIA), enzyme
linked immunosorbent assay (ELISA), and immunofluorescence assay (IFA) e.g.
HIV can be quantified by the levels of p24 (capsid) antigen in the culture fluid
or blood
• Molecular Assay - Viral genomes, both RNA and DNA, can be quantified to
determine the amount of virus (viral load) in blood eg PCR is used to
determine viral load in HIV
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COMMON DNA VIRUSES
• Pox virus- cause small pox, cow pox, monkey pox
• Human Papilloma Virus- cause warts, tumors and cancers.
• Hepatitis B
• Herpes virus-
• cause oral lesions cold soles, fever, blisters.
• Herpes zoster- causes shingles which follows the nerve part of the body
infected and common in HIV/AIDS.
• Adeno virus- cause conjunctivitis, respiratory infection eg pharyngitis,
running nose fever, pneumonia and some tumors.

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COMMON RNA VIRUSES
• Notable human diseases caused by RNA viruses include:- the common
cold, influenza, SARS, MERS, Covid-19, Dengue Virus, hepatitis
C, hepatitis E, Ebola virus disease, rabies, polio, mumps, and measles

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Selected viruses of medical
importance

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ROTAVIRUS
• Reoviridae family
• Wheel-like non-enveloped
double shelled virus with
icosahedral symmetry
• Comprises double stranded
segmented RNA
• 11 segments of RNA

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Rotavirus cont’d
• Classified into 7 sero-groups; A --> G
• Group A is most common and has 2 subgroups (I and II) based on
antigenic structure of inner capsid protein VP2
• Serotype based on outer capsid proteins VP7 (G Serotype) and VP4 (P
serotype)
• P gp :8 serotypes
• G gp: 10 serotypes
• Prevalent viruses: P8G1, P8G3, P8G4,P4G2

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Rotavirus cont’d
• Acute diarrhea is a leading cause of mortality in the world in children
<5 years
• > 1 billion cases per annum
• 5 – 10 million deaths
• Single most important cause of severe dehydrating diarrhea in early
childhood is rotavirus infection
• Other viruses: astrovirus, adenovirus, caliciviruses (norwalk)

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EPIDEMIOLOGY
• Rotavirus causes disease in all animals and birds
• Group A commonest pathogen in man
• Group B associated with severe disease affecting infants and adults in
China only
• Group C causes occasional human outbreaks
• Other groups are mainly animal strains
• Fears of antigenic variability from antigenic drifts and re-assortments
during super-infection by different strains
• In Africa unusual variants of serotype G and P have been found
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Epidemiology cont.
• In the tropics disease peaks during hot dry seasons
• Most affected age 3 – 24months
• Trans-placental and breastmilk antibodies are protective < 3months of
age
• Neonatal and adult infections commonly asymptomatic

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TRANSMISSION
• Fecal –oral route
• Outbreaks common in children’s hospitals and child-care centers
• Virus shed in stool in high concentrations before and 2 – 12 days after
clinical illness; longer in malnourished children
• Highly infectious virus
• Resistant to water chlorination

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PATHOGENESIS
• Infect and destroy villus tips in the small intestine
• Upper two thirds of duodenum affected but viral particles are
released and undergo replication at distal sites
• Incubation: less than 48hours
• Begins commonly with fever, vomiting then abrupt frequent watery
stools. Diarrhea lasts approx 5 – 7 days
• Dehydration develops and progresses very fast in infants
• More severe disease in children with malnutrition and concurrent
intestinal disease

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Pathogenesis and patho-physiology
• Pathogenicity attributed to enterotoxin NSP4
• Selective infection of the cells on the villus tips and subsequent lysis
from the toxin leads to
1. Increased secretion of intestinal fluid
2. Mal-absorption primarily of lactose
• Extra-intestinal disease rare in normal host; hepatic and renal
involvement may occur in immuno-compromised host

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DIAGNOSIS
• Based on stool analysis
• Latex agglutination
• RT-PCR viral RNA
• ELISA for antigen detection
• Immuno-electron microscopy

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Rotavirus vaccines
Rotarix
• Serotype P8G1
• 2 doses
• 1st dose between 6 and 14 weeks
• 2nd dose by 24weeks
• Minimum interval between doses
required to be at least 4 weeks
• Storage conditions: 2– 8 degrees
centigrade and away from light
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Rotateq
• Also oral live attenuated vaccine
• Human- bovine re-assortant
pentavalent vaccine
• Serotypes human G14, P1a, bovine
G6, P7
• Given in 3 doses: 1st between age 6
and 12 weeks; two other doses at
interval of 4 – 10 weeks. Last dose by
age 32 weeks
• Cold chain similar to rotarix
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Picornavirus family
• The picornavirus family includes two groups of medical importance:
• The enteroviruses and the rhinoviruses.
• Among the major enteroviruses are poliovirus, coxsackie viruses,
echoviruses, and hepatitis A virus

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Polio
• Poliovirus is transmitted by oral-fecal contact.
• During epidemics, it also may be transmitted by pharyngeal spread
• 90 to 95% of poliovirus infections are asymptomatic.
• There is an incubation period of 7 to 14 days, during which the virus
undergoes primary replication in the lymphatic tissues of the GI tract.
• An asymptomatic primary (minor) transient viremia occurs, with spread of
virus to the systemic reticuloendothelial tissue.
• In 4 to 8% of individuals, a second major viremia occurs, causing symptoms
of the "minor illness" (abortive polio), which resembles the usual viral
infection, including headache, sore throat, fever, nausea, vomiting, malaise,
and fatigue.
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Polio cont’d
• In a fraction of those with major viremia and abortive polio,
involvement of the central nervous system then occurs, usually after a
symptom-free interval of a few days.
• This usually is signaled by signs and symptoms of meningitis, including
neck stiffness, headache, fever, and vomiting.
• In some of these patients, the poliovirus then causes selective
destruction of motor neurons, characterized by severe back, neck,
and muscle pain, and the development of motor weakness.
• This paralysis occurs in only about 0.1 percent of all poliovirus
infections
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Polio pathogenesis
• It may occur by direct passage of the virus from blood by crossing the
blood-brain barrier, or may occur by retrograde axonal transport from
muscle to spinal cord and brain.
• After invading the central nervous system, the virus uncoats, viral
replication occurs, and the motor neuron dies, leading to paralysis of
muscle fibers supplied by this motor neuron.
• Spread of the virus to neighboring motor neurons may occur laterally,
independent of axonal transport, or by trans-neuronal spread, in a
retrograde transport dependent fashion
• Other neurons can be infected as well, producing brainstem encephalitis
and respiratory insufficiency
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Polio Clinical presentation
• Weakness may vary from one muscle or group of muscles, to quadriplegia, and respiratory
failure.
• Tone is reduced, nearly always in an asymmetric manner.
• Proximal muscles usually are affected more than distal ones and legs more commonly than arms.
• Reflexes are decreased or absent.
• The sensory examination is normal.
• Weakness typically worsens over two to three days, although sometimes worsening can progress
for up to a week.
• Bulbar involvement occurs in 5 to 35 percent of patients, producing dysphagia, dysarthria, and
difficulty handling secretions.
• There may be encephalitis, usually in infancy.
• Respiratory insufficiency may occur

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Diagnosis
• The diagnosis of poliomyelitis is suspected based on the clinical presentation and
cerebrospinal fluid findings.
• The cerebrospinal fluid shows a pleocytosis as in other types of aseptic meningitis, initially
characterized by polymorphonuclear leukocytes, followed by a shift to lymphocytes.
• The cerebrospinal fluid protein is usually elevated.
• The diagnosis can be confirmed by virus isolation.
• Poliovirus can be isolated from throat secretions in the first week of illness, and from feces
for several weeks.
• It rarely can be isolated from cerebrospinal fluid.
• The diagnosis can also be confirmed by polymerase chain reaction amplification of
poliovirus RNA from cerebrospinal fluid or serologically, by comparing viral titers in acute
and convalescent sera

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Treatment
• Treatment of poliomyelitis is supportive, including pain relief and
physical therapy.
• Respiratory failure may develop, requiring mechanical ventilation.
• Patients with bulbar involvement require close monitoring of
cardiovascular status because of the association with blood pressure
fluctuations, circulatory collapse, and autonomic dysfunction
• Such patients may require intubation for airway protection
• Post-polio syndrome may occur many years after the acute episode,
and has been defined as the "onset of functional deterioration after a
prolonged period of stability" in patients with a history of polio
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Polio vaccination
• Because there are no effective treatments to restore motor neuron
function after paralytic polio, prevention has been a mainstay of
clinical and research efforts
• Jonas Salk created the inactivated poliovirus vaccine (IPV), using killed
virus in 1952.
• The Sabin oral poliovirus vaccine (OPV), using live attenuated virus,
proved successful in 1960, and replaced the Salk vaccine in 1962

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Measles virus
• Causes an acute, highly contagious respiratory disease called measles
• The disease is also called rubeola
• Globally, an estimate of 254,928 measles cases and 89,780 deaths
occur annually.

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Measles virus biology
• Member of the family Paramyxoviridae, genus Morbillivirus.
• RNA virus, Enveloped , Spherical, Non-segmented
• Single-stranded
• Negative-sense
• Contains 6 structural proteins;
• 3 complexed to RNA &
• 3 associated with viral membrane envelope
• Only one serotype & no subtypes recognised.

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• Of the 6 major structural proteins of measles virus, the 2 most important in terms
of induction of immunity are: hemagglutinin (H) protein & the fusion (F) protein.
• The neutralizing antibodies are directed against the H protein, and antibodies to
the F protein limit proliferation of the virus during infection
• Fusion Protein (F) mediates:
o fusion of virus & host cell membranes expressing CD46 complement receptor.
o viral penetration & hemolysis.
o fusion of infected cells to form syncytium (multinucleated giant cell).
• Hemagglutinin Protein (H) mediates:
o adsorption of virus to cells.
o The main neutralising Ag.
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 MEASLES VIRUS

11/24/2023 Dr. Keli 69

EPIDEMIOLOGY
• Remains a leading cause of death in young children globally, despite the
availability of a safe & effective vaccine.
• In 1980, before widespread vaccination, measles caused an estimated 2.6 million
deaths each year.
• More than 95% of measles deaths occur in low-income countries with weak
health infrastructures.
• There are no known measles virus reservoirs outside of humans.
• Most cases are from Africa and failure to vaccinate has been identified as the
primary cause.
• Measles vaccination resulted in a 74% drop in measles deaths from 535,300 in
2000 to 139,300 in 2010 worldwide.
11/24/2023 Dr. Keli 70
Transmission
• The portal of entry is through the respiratory tract or conjunctivae
following contact with large droplets or small droplet aerosols in
which virus is suspended.
• Is highly contagious—attack rate in a susceptible individual exposed to
measles is 75 percent, 90% of people without immunity sharing a
house with an infected person will catch it.
• Average incubation period of 14 days (range 6-19 days)
• Infectivity lasts from 2-4 days prior to 2-5 days following the onset of
the rash

11/24/2023 Dr. Keli 71

Groups At Risk
• Children too young to be vaccinated.
• Individuals who were never vaccinated.
• Individuals for whom the vaccine failed to elicit a protective immune response.
• Individuals in contact with ill persons .
• Children born to HIV seropositive mothers.
• Individuals with vit. A deficiency.
• Persons travelling to endemic areas.
• Infants who lose passive antibody prior to the age of routine immunization.
• People living in overcrowded areas.
• Malnourished individuals.
• Pregnant women.
11/24/2023 Dr. Keli 72
Clinical Manifestations
• Measles is characterized by fever, malaise, rash, cough, coryza (acute
rhinitis), conjunctivitis and enanthem (rash on mucous membranes)

• Measles has 4 clinical stages:

• Incubation stage
• Prodromal stage
• Exanthem
• Recovery

11/24/2023 Dr. Keli 73

Differential Diagnosis.
• Typical measles is unlikely to be confused with other illnesses,
especially if Koplik spots are observed.
• Measles in the later stages or inapparent or subclinical cases may be
confused other exanthematous immune-mediated illnesses and
infections.
• Rubella, Adenoviruses, Enteroviruses, EBV, Exanthem subitum (in
infants), Erythema infectiosum (in older children), Mycoplasma
pneumoniae, Group A streptococcus infection, Kawasaki syndrome,
Drug eruptions

11/24/2023 Dr. Keli 74

Diagnosis Of Measles
1. Most cases are diagnosed clinically,
• Clinical case definition: Generalized rash > 3days
• Temp 38.3’
• 3 C’s: conjunctivitis, cough, coryza
2. Microscopy - of multinucleate giant cells with inclusion bodies detectable in
nasopharyngeal secretions
3. Direct and indirect immunofluorescence - Used to demonstrate MV
antigens in cells from NPS specimens.
4. Viral isolation: from throat or conjunctival washings, sputum, urinary
sediment cells & lymphocytes
5. Serology: measles-specific IgM is found via ELISA.
11/24/2023 Dr. Keli 75
COMPLICATIONS
• Largely attributable to the pathogenic effects of the virus on the
respiratory tract and immune system
• Risk factors for complications
• Age<5 yr (especially <1 yr), >20 yr
• Overcrowding- larger inoculum dose following household exposure
• Severe malnutrition-suboptimal immune response
• Low serum retinol levels

11/24/2023 Dr. Keli 76

Measles complications cont’d
• Acute otitis media - most common complication
• Pneumonia - Most common cause of death.
• Measles encephalitis in immunocompromised patients results from direct
damage to the brain by the virus
• Presents 1–10 months following measles
• Signs and symptoms include seizures, myoclonus, stupor, and coma
• Croup, tracheitis, and bronchiolitis
• Retropharyngeal abscess
• Measles in pregnancy is assoc with high maternal morbidity, fetal wastage and
stillbirths, and congenital malformations in 3% of live born infants

11/24/2023 Dr. Keli 77

Measles complications cont’d
• Diarrhea and vomiting – Dehydration
• Appendicitis due to obstruction of the appendiceal lumen by lymphoid
hyperplasia.
• Febrile seizures occur in <3% of children with measles
• Keratitis, appearing as multiple punctate epithelial foci
• Myocarditis
• Hemorrhagic or “black measles
• Thrombocytopenia
• Bacteremia, cellulitis, and toxic shock syndrome

11/24/2023 Dr. Keli 78

Prevention.
MEASLES VACCINE (Kenya)
• Live attenuated vaccine
• Confers CMI
• Storage: freeze dried heat sensitive vaccine 2-8 degrees
• Dose:0.5 mls at 9months of age
• Route of admin: Subcut,on the deltoid muscle of the upper arm
• Efficacy:>95%
• Discard after 6 hours of use
• S/E: low grade fever, mild rash
11/24/2023 Dr. Keli 79
Measles vaccine
• Dvlpd as live attenuated vaccine in 1954 – Enders & Peebles
• Edmonstron B strain – had S/E fever and rash
• Schwarz further attenuated it.
• Licensed in 1963 for use worldwide.
• Seroconversion rate in kenya is 92% by 9months but in US 86% by 9-
11mo. &95%by 12mo.

11/24/2023 Dr. Keli 80

Vaccination (MMR)
• Vaccines are Live attenuated
containing Edmonston B or Schwartz
strains which give seroconversion rate
of 90%.
• The immunity may be life long.
• The measles vaccine is often
incorporated w/ rubella and/or
mumps vaccines in countries where
these illnesses are problems.
• Its equally effective in the single or
combined form

11/24/2023 Dr. Keli 81

Post-exposure prophylaxis
• Susceptible people exposed to disease may be protected from infection by
vaccine admin or immunization w/ Ig.
• The vaccine is effective in prevention or modification of measles if given
within 72 hr of exposure.
• Immune globulin may be given up to 6 days following exposure to prevent or
modify infection.
• Immuno-competent children: 0.25 mL/kg IM &
• ISS children : 0.5 mL/kg.
• Immune globulin is indicated for susceptible household contacts of measles
patients, esp infants <6 mo of age, pregnant women, and immuno-
compromised persons.
11/24/2023 Dr. Keli 82
Mumps
Definition:
• Acute generalized paramyxovirus infection usually presenting with
unilateral or bilateral parotitis.
• Incubation is approximately 14 to 24 days.

• Signs and symptoms:

• Parotid pain and swelling in one or both glands
• Rare prodrome of fever, neck muscle ache, malaise
• Initial parotid swelling just behind jaw
• Swelling peaks in 1-3 days, lasts 3-7 days
11/24/2023 Dr. Keli 83
Mumps virus
• Genus Paramyxovirus, member of the
family Paramyxoviridae.
• This virus contains a single-stranded,
negative-sense RNA surrounded by a
glycoprotein envelope.
• Of 2 glycoproteins on the surface of
the RNA viral envelope, one mediates
neuraminidase and hemagglutination
activity,
• whereas the other is responsible for
fusion to the lipid membrane of the
host cell.
11/24/2023 Dr. Keli 84
Treatment and prevention
• Adequate attention to hydration and alimentation is essential.
• The diet should be light, with a generous offering of fluids.
• May use acetaminophen for fever and/or pain.
• Mumps may improve with corticosteroids or a non-steroidal anti-
inflammatory
• Attenuated live mumps virus vaccine is used routinely in the
immunization of children, adolescents, and young adults.

11/24/2023 Dr. Keli 85

Influenza virus
• Influenza viruses are the only
members of the orthomyxovirus
family.
• Influenza A, B, C and D.

11/24/2023 Dr. Keli 86

Influenza virus
• The orthomyxoviruses differ from the paramyxoviruses primarily in that the
former have a segmented RNA genome (usually eight pieces), whereas the
RNA genome of the latter consists of a single piece.
• Influenza viruses, especially influenza A virus, show changes in the
antigenicity of their hemagglutinin and neuraminidase proteins;
• this property contributes to their capacity to cause devastating worldwide
epidemics.
• There are two types of antigenic changes:
(1) antigenic shifts, which are major changes based on the reassortment of segments
of the genome RNA
(2) antigenic drifts, which are minor changes based on mutations in the genome RNA.
11/24/2023 Dr. Keli 87
• Many species of animals (e.g., aquatic birds, chickens, swine, and
horses) have their own influenza A viruses.
• These animal viruses are the source of the RNA segments that encode
the antigenic shift variants that cause epidemics among humans.
• For example, if an avian and a human influenza A virus infect the same
cell.
• H3N2 is the designation of the hemagglutinin (H) and neuraminidase
(N) types.
• Current; H1N1, H3N2. (Included in current vaccine).
• Prevention: Vaccines
11/24/2023 Dr. Keli 88
11/24/2023 Dr. Keli 89
Coronaviruses
• Coronaviruses are large, enveloped RNA viruses.
• The human coronaviruses cause common colds and have been
implicated in gastroenteritis in infants.
• A novel coronavirus was identified as the cause of a worldwide
outbreak of a severe acute respiratory syndrome (SARS) in 2003 then
in 2019 (SARS-COV2).
• Coronaviruses are enveloped, 120-to 160-nm particles that contain an
unsegmented genome of single-stranded positive-sense RNA (27–32
kb), the largest genome among RNA viruses

11/24/2023 Dr. Keli 90

11/24/2023 Dr. Keli 91
Coronaviruses
• Discuss
• Lab dx; Nucleic acid and antigen
• Treatment, prevention and control

11/24/2023 Dr. Keli 92

HIV (Human Immunodeficiency Virus)
• HIV is a member of the lentivirus family of animal retroviruses.
• Discovered in 1981
• Two closely related types of HIV, designated HIV-1 and HIV-2, have
been identified.
• AIDS - Acquired immunodeficiency syndrome – clinical syndrome
manifested by opportunistic infections due to breakdown in the
immune system.
• Major deficiency is a quantitative decrease in T helper cell

11/24/2023 Dr. Keli 93

• HIV – 1
• Is found worldwide
• Is the main cause of the worldwide pandemic
• HIV – 2
• Is mainly found in West Africa, Mozambique and Angola.
• Causes a similar illness to HIV – 1
• Less efficiently transmissible rarely causing vertical transmission
• Less aggressive with slower disease progression

• Phylogenetic evidence indicates origins of HIV from non-human primates

(HIV-1 isolated from common chimpanzee (closest to humans), HIV-2
isolated from sooty mangabey) - Zoonotic origin?
11/24/2023 Dr. Keli 94
Kenyan Situation
• First case of AIDS diagnosed in Kenya in 1984
• Now 2.2 million HIV+,
• AIDS declared National disaster 1999
• Prevalence (2018) 4.9%, Women > Men
• Annual incidence 0.14% among adults

11/24/2023 Dr. Keli 95

HIV Biology
• Family- retroviridae
• Genus- lentivirus
• Enveloped, diploid,
• Viral particle is spherical in shape
• has a D of 80-100nm
• single-stranded, positive-sense RNA viruses with a DNA intermediate
incorporated into the host-cell DNA

11/24/2023 Dr. Keli 96

HIV-1 Characteristics
• A lentivirus (within Retrovirdae family)
• ss(+)RNA genome
• Structural genes + Regulatory genes
• Virus core cylindrical (encases viral enzymes such as RT, protease and
integrase)
• Surrounding the core is envelope protein (heavily glycosylated)
• Replication is via integration into host genome
• Major target is T-helper lymphocytes and cells of monocyte-
macrophage lineage (CD4-containing cells)
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HIV-1 Proteins & Functions
• Matrix protein MA) - lines envelope
• Capsid protein (CA) - protects the core; most abundant protein in virus particle
• Nucleocapsid (NC) - protects the genome; forms core
• Protease (PR) - gag protein cleavage at maturation
• Reverse transcriptase (RT) - Reverse transcribes the RNA genome; also has
RNAseH activity
• Integrase (IN) - integration of provirus
• Surface glycoprotein (SU)- The outer envelope glycoprotein; major virus antigen
• Transmembrane (TM) protein - inner component of the mature envelope
glycoprotein

11/24/2023 Dr. Keli 98

 HIV Structure and Genes
 2 identical single strands of RNA
packaged within a core of viral
proteins surrounded by a
phospholipid bilayer envelop
derived from the host cell
membrane.
 The lipid membrane is lined by a
matrix protein.
 The lipid membrane is studded
with the surface glycoprotein (gp)
120 and the transmembrane gp
41 protein.
 These glycoprotein spikes
surround the cone-shaped
protein core.
11/24/2023 Dr. Keli 99
HIV Structure and Genes
• The gp120 and gp41 mediate the entry of virus into the host cells.
• The core (capsid) is made up of several proteins:-P24 the main protein
• Within the capsid are two identical single strands of RNA (the viral genetic
material).
• The most important viral enzymes are Reverse Transcriptase (RT), Protease and
Integrase.
o RT converts viral single-stranded RNA into a double stranded deoxyribonucleic acid
(DNA).
o DNA is incorporated into host nucleus as the proviral DNA.
o Integrase facilitates integration of the DNA into the host’s chromosomal DNA.
o Protease enzyme splits generated macro-proteins into smaller viral proteins (core,
envelope & regulatory proteins and enzymes) which go into forming new viral particles.

11/24/2023 Dr. Keli 100

HIV Structure and Genes
• RNA genome of HIV has same basic arrangement of nucleic acid sequence
characteristic of all known retroviruses.
• Long terminal repeats (LTRs) at each end of the genome regulate viral gene
expression, viral integration into the host genome, and viral replication.
• The gag sequences encode core structural proteins.
• The env sequences encode the envelope glycoproteins gp120 and gp41, which are
required for infection of cells.
• The pol sequences encode reverse transcriptase, integrase, and viral protease
enzymes required for viral replication.
• In addition to these typical retrovirus genes, HIV-1 also includes six other regulatory
genes, namely, the tat, rev, vif, vpr, and vpu genes whose products regulate viral
replication in various ways.
11/24/2023 Dr. Keli 101
HIV Life Cycle
 Binding, Fusion
and Entry
 Transcription
 Integration &
Replication
 Budding
 Maturation

11/24/2023 Dr. Keli 102

Retrovirus life cycle – summary
1. Host cell CD4 (viral receptor) bind to viral Envelope gp
2. Viral envelope fuses with cell membrane - viral capsid enters cell.
3. Capsid opened - viral (+) RNA, RT, & tRNA primers released in host cell.
4. (+)RNA -> dsDNA genome (via RT)
5. dsDNA (viral genome) integrated in host cell chromosome.
6. Integrated provirus DNA is transcribed to produce (+) RNA.
7. (+) RNA translated -> viral proteins (RT, capsid proteins, Env gp).
8. New virus particles assembled. Two copies of (+) RNA, two RT, and two tRNA
primers packaged per capsid.
9. Progeny virus bud off from the cell by exocytosis, thus forming the viral envelope.

11/24/2023 Dr. Keli 103

HIV-1 Pathogenesis
HIV infects CD4 cells

Disseminated infection

Specific immune Response (Ab, CMI)

Clearance of most virus

Some persistence
a) Gradual loss of CD4 cells
b) Destruction of microenvironment of lymphoid tissue
11/24/2023 Dr. Keli 104
HIV-1 Transmission
(1) Blood products
• Blood transfusions
• Intra-venous drug abusers - sharing of needles
• Health care workers: - needlestick injuries
(2) Organ transplants
(3) Sexual intercourse
(4) Vertical Transmission
• 10-40% of babies born of HIV-infected mothers will be infected.
• Infection may occur (a) in utero (b) during birth (c) post-natally, through
breast feeding
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Pathogenesis of HIV infection and AIDS
• The female genital tract is the primary route for heterosexual transmission of
HIV .
• During male-to-female transmission, virus in semen, either cell-free or cell-
associated, penetrates the stratified squamous epithelium of the vagina or the
columnar epithelium of the endocervix to infect cells within or below the
epithelium
• This is followed by dissemination of the virus to lymphoid organs, particularly
gut-associated lymphoid tissues (GALT), within the first few days after infection
• Presence of other genital infections, including STIs, can enhance HIV
susceptibility either by breaching the epithelial barrier, recruiting HIV target cells
to the genital tract, or by generating a pro-inflammatory local immune milieu

11/24/2023 Dr. Keli 106

Pathogenesis of HIV cont’d
• Initially an acute infection (which is only partly controlled by the adaptive immune
response) that advances to chronic progressive infection of peripheral lymphoid
tissues
• Acute(early) infection is characterized by infection of memory CD4+ T cells (which
express CCR5) in mucosal lymphoid tissues, and death of many infected cells.
• The transition from the acute phase to a chronic phase of infection is characterized
by dissemination of the virus, viremia, and the development of host immune
responses.
• Dendritic cells in epithelia at sites of virus entry capture the virus and then migrate
into lymph nodes.
• In the next, chronic phase of the disease, lymph nodes and the spleen are sites of
continuous HIV replication and cell destruction
11/24/2023 Dr. Keli 107
Immune response to HIV
• HIV infection ultimately results in impaired function of both adaptive and
innate immune systems
• Most important prominent defects are in cell mediated immunity
• An important cause of loss of CD4+ T cells is the direct cytopathic effect of
infection of these cells
• HIV specific humoral and cell mediated immune responses develop following
infection but generally provide limited protection
• Initial adaptive immune response characterized by expansion of CD8+ T cells
specific for HIV peptides
• Antibody responses to a variety of HIV antigens are detectable within 6 to 9
weeks after infection.
11/24/2023 Dr. Keli 108
Mechanism of Immune Evasion by HIV
• Failure of cell mediated and humoral immune responses to eradicate HIV
infection multifactorial.
• Importantly, depletion and functional inhibition of CD4+ T cells, the
immune responses may be too compromised to eliminate the virus.
• In addition
• HIV has an extremely high mutation rate because of error-prone reverse
transcription
• HIV infected cells may evade CTLs through down regulation of class I MHC
molecule expression
• HIV infection may inhibit cell mediated immunity (Th2 cells specific for HIV and
other microbes may expand relative to Th1 cells. Th2 cytokines inhibit cell
mediated immunity)
11/24/2023 Dr. Keli 109
Clinical features - HIV
• Primary infection
• flu-like illness (coincides with seroconversion, between 2 and 4 weeks post
exposure)
• Symptoms include, fever, night sweats, sore throat, lymphadenopathy,
diarrhea
• Asymptomatic phase
• variable (2-10 yrs - Patients are clinically well, but infectious)
• Prodromal phase
• weight loss, fever, persistent lymphadenopathy, oral candidiasis and diarrhea.
These symptoms precede the progression to AIDS.

11/24/2023 Dr. Keli 110

Clinical features - AIDS
Acquired Immunodeficiency Syndrome (AIDS)
• Syndrome with the following features:
1) Constitutional disease: fever, diarrhea, weight loss, skin rashes
2) Neurological disease: dementia, myelopathy, peripheral
neuropathy
3) Immunodeficiency: Increased susceptibility to opportunistic
infections
4) Rare malignancies: Kaposi sarcoma, oral hairy leukoplakia,
lymphomas.

11/24/2023 Dr. Keli 111

 Staging – clinical

11/24/2023 Dr. Keli 112

Opportunistic Infections
• HIV does not directly kill those it infects, instead it ravages their
immune system allowing the entry of opportunistic infections, to
which most patients eventually succumb.
• Even in the era of effective ART, OIs remain the most common cause
of morbidity and mortality in HIV patients.
• The prevention and management of OIs remain important in the care
of the HIV pt whether or not they have access to ARV drugs.

11/24/2023 Dr. Keli 113

 Opportunistic infections

11/24/2023 Dr. Keli 114 114

Opportunistic Infections
• Oral candidiasis • Herpes zoster

11/24/2023 Dr. Keli 115

Opportunistic Infections
• Kaposi sarcoma

11/24/2023 Dr. Keli 116

HIV Laboratory diagnosis
• Serologic tests: detect HIV antibodies in blood and other body fluids
1.ELISA
2.Rapid tests (determine and unigold)
• IgG develops 4-6 weeks post exposure and remains detectable for life
• Its presence in serum therefore indicates infection. Exception: Uninfected infants of HIV
positive mothers

• Virologic tests: detect HIV DNA, RNA or viral antigen

1.RNA PCR
2.DNA PCR
3.HIV p24 antigen
4.Viral cultures
11/24/2023 Dr. Keli 117
Therapy of HIV infection
• "Highly Active Antiretroviral Therapy” or HAART = drugs used in
combination to treat HIV infection
1.Nucleoside-Analog Reverse Transcriptase Inhibitors (NRTI) - inhibit
viral RT and are incorporated into viral DNA (they are chain-
terminating drugs)
Examples: (a) Zidovudine (AZT = ZDV, Retrovir) (b) Didanosine (ddI,
Videx) (c) Zalcitabine (ddC, Hivid) (d) Stavudine (d4T, Zerit) (e)
Lamivudine (3TC, Epivir)

11/24/2023 Dr. Keli 118

Therapy of HIV infection (2)
2. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) – bind to
RT (compromises function) Examples: Nevirapine (Viramune) &
Delavirdine (Rescriptor)
3. Protease Inhibitors (PI) – inhibit protease (hence no maturation of
virus particles)
Examples: Saquinavir (Invirase), Ritonavir (Norvir), Indinavir
(Crixivan) & Nelfinavir (Viracept)
4. Fusion inhibitors - (interfere with binding & fusion) - Examples: "T-
20" and "T1249"
5. CCR5 antagonists - against R5-tropic viruses
11/24/2023 Dr. Keli 119
HIV Vaccine prospects
• No effective vaccine available for HIV
• Attempts to develop a vaccine, using:
• purified viral envelope glycoproteins, gp120 or 160
• whole inactivated virus
• live attenuated HIV strains (lacking certain genes)
• live recombinant virus vectors, expressing HIV proteins
• Neut. Ab in the serum does not protect HIV infection: Possible reasons for this
include:
• Antibody enhancement of infection
• Rapid virus mutation may result in variation of envelope antigens (escape mutants)
• HIV can infect cells in privileged sites (e.g. brain)
• Host may be infected by whole virus-infected cells
11/24/2023 Dr. Keli 120
HIV Prevention
• Voluntary counseling and testing (VCT)
– Risk assessment
– Risk reduction
– Testing
• Behavioral interventions to reduce risk behavior
• Condoms
• Sexually transmitted infection (STI) prevention and treatment
• Antiretroviral (ARV) and breastfeeding interventions to prevent
mother-to-child transmission (MTCT)
• Safe transfusion practices

11/24/2023 Dr. Keli 121

11/24/2023 Dr. Keli 122
Herpesvirus family
The herpesvirus family contains six important human pathogens:
• Herpes simplex virus (HSV)- type 1 (HHV-1)
• Herpes Simplex Virus type 2 (HHV-2)
• Varicella-zoster virus ( VZV, or HHV-3) - chickenpox
• Epstein-Barr virus (EBV, or HHV-4) – infectious mononucleosis
• Cytomegalovirus (CMV, or HHV-5)
• HHV-8 (Kaposi sarcoma–associated virus)
• HHV-6
• HHV-7
11/24/2023 Dr. Keli 123
HHVs - Human herpes viruses
• Core - linear double-strand DNA
• Icosahedral capsid 100–110 nm in diameter
• Envelope containing viral glycoprotein spikes on the surface
• Transcription, genome replication, and capsid assembly occur in the
host cell nucleus.
• Genes are replicated in a specific order: (1) immediate-early genes,
which encode regulatory proteins; (2) early genes, which encode
enzymes for replicating viral DNA; and (3) late genes, which encode
structural proteins

11/24/2023 Dr. Keli 124

Herpes Simplex Virus
• Herpes simplex is an acute, self-limiting, intraepidermal vesicular
eruption caused by HSV.
• HSV is a medium-sized DNA virus that replicates within the nucleus.
• Based on culture and immunologic characteristics, it is divided into
two types: HSV-1 and HSV-2.
• Usually, HSV-1 causes oral infection and HSV-2 causes genital
infection.

11/24/2023 Dr. Keli 125

Herpes simplex virus cont’d
• Primary infection with HSV-1 usually occurs in children, in whom it is
subclinical in 90% of cases.
• The remaining 10% of infected children have acute gingivostomatitis.
• HSV-2 primary infection usually occurs after sexual contact in
postpubertal individuals, and it produces acute vulvovaginitis or
progenitalis.
• The risk of recurrence after primary genital infections is less with HSV-
1 (14%) than with HSV-2 (60%).

11/24/2023 Dr. Keli 126

Pathogenesis
• Most transmission occurs when persons shed virus.
• Usually skin-skin, skin-mucosa, mucosa-skin contact.
• Primary HSV infection occurs through close contact with a person shedding
virus at a peripheral site, mucosal surface, or secretion.
• Infection occurs via inoculation onto susceptible mucosal surface or break in
skin.
• HSV replicates in parabasal and intermediate epithelial cells, causing lysis of
infected cells, vesicle formation, and local inflammation.
• After primary infection at inoculation site, HSV ascends peripheral sensory
nerves and enters sensory (trigeminal, cervical, or lumbosacral) or autonomic
nerve root (vagal) ganglia, where latency is established.
11/24/2023 Dr. Keli 127
Presentation
• Indurated erythema followed by grouped vesicles on an erythematous base is typical of
herpes infections.
• The vesicles quickly become pustules, which rupture, weep, and crust.
• Affected skin sometimes becomes necrotic, resulting in punched-out ulceration.
• Primary infections – gingivostomatitis or vulvovaginitis – are characterized by extensive
vesiculation of the mucous membranes. This results in erosions, necrosis, and a marked
purulent discharge.
• Primary infections are frequently accompanied by systemic symptoms that include fever,
malaise, myalgia, headache, and regional adenopathy.
• Localized pain and burning may be so severe that drinking and eating, or urinating, may be
compromised.
• Herpes infection can develop in any area where inoculation has occurred. Recurrent herpes
infections are characterized by localized grouped vesicles in the same location.
11/24/2023 Dr. Keli 128
• Herpetic whitlow is infection of the fingers. This is an occupational
hazard of medical and dental personnel that can be prevented by
wearing gloves.

• Traumatic herpes simplex has been reported in epidemics among

wrestlers (herpes gladiatorum).

• Eczema herpeticum is a generalized cutaneous infection with HSV in

individuals with predisposing skin diseases such as atopic dermatitis.
It is accompanied by severe toxic symptoms and may be fatal.
11/24/2023 Dr. Keli 129
Precipitating Factors for Recurrence
• Skin/mucosal irritation (UV radiation), altered hormones
(menstruation), fever, common cold, altered immune states, site of
infection (genital herpes recurs more frequently than labial).

• Approximately one-third of persons who develop herpes labialis will

experience a recurrence; of these, one-half will experience at least
two recurrences annually.

11/24/2023 Dr. Keli 130

Herpes simplex virus infection

Herpes simplex virus infection: primary

recurrent herpes labialis
gingivostomatitis
11/24/2023 Dr. Keli 131
Herpes simplex virus infection

Herpes simplex virus infection: herpetic whitlow

11/24/2023 Dr. Keli 132

Lab Dx
I. Culture-Diagnostic

II. Direct microscopy of fluid from vesicle

III. Antigen detection (2-6 wks to develop)

IV. Polymerase chain rxn - evidence of viral dna

V. Serology: ELISA - Monoclonal antibodies specific for HSV-1 and HSV-2

antigens.
11/24/2023 Dr. Keli 133
Lab Diagnosis cont’d
• Direct Microscopy: Tzanck Smear
• Fluid from intact vesicle is smeared thinly on a microscope slide,
dried, and stained with either Wright's or Giemsa's stain.
• Positive, if acantholytic keratinocytes or multinucleated giant
acantholytic keratinocytes (TZANCK CELLS) are detected.
• Positive in 75% of early cases, either primary or recurrent.

11/24/2023 Dr. Keli 134

Management
• Prevention Skin-to-skin contact should be avoided during outbreak of
cutaneous HSV infection.
• Topical Antiviral Therapy Approved for herpes labialis; minimal efficacy.
1. Acyclovir 5% ointment
2. Penciclovir 1% Cream for recurrent orolabial infection in immunocompetent
individuals.
• Oral Antiviral Therapy for use in genital herpeS: acyclovir, valacyclovir, and
penciclovir.
• For severe disease, IV acyclovir therapy may be required.
• Foscarnet - For severe disease caused by proven or suspected acyclovir-
resistant strains, hospitalization should be considered.
11/24/2023 Dr. Keli 135
Hepatitis Viruses
• Hepatitis viruses A, B, C, D (HAV, HBV, HCV, HDV [which requires
coexisting HBV infection]), and E (HEV) cause the majority of clinical
cases of viral hepatitis.
• Whether hepatitis G virus (HGV) is pathogenic in humans remains
unclear.

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HEP A
• Member of the Picornaviridae family
• RNA virus
• Transmission: mainly FEACO-ORAL. Also sexual (anal-oral) contact
• Transmission by blood transfusion is rare.
• Maternal-neonatal transmission: not established.
• Dx marker: detection of anti-HAV IgM ab

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HEP B
• Hepadnaviridae family, double stranded DNA virus
• The complete virion (Dane particle) has a viral core particle consisting
of a nucleocapsid (HBcAg), which surrounds HBV DNA, and DNA
polymerase. The nucleocapsid is coated with HBsAg
• HBsAg: found in circulation
• HBcAg: not found circulation but in hepatocytes
(immunohistochemical staining of infected liver tissue)

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HBV
• HBV is readily detected in serum, seen at very low levels in semen,
vaginal mucus, saliva, and tears.
• Not detected in urine, stool, or sweat.
• Can survive storage at –20°C (–4°F) and heating at 60°C (140°F) for 4
hours.
• Inactivated by heating at 100°C (212°F) for 10 minutes or by washing
with sodium hypochlorite (bleach).

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HBV
• Transmitted both parenterally and sexually, most often by mucous
membrane exposure or percutaneous exposure to infectious body
fluids.
• Saliva, tears, serum, breast milk and semen: all infectious.
• Percutaneous exposures leading to transmission: transfusion of
blood/blood products, injection drug use with shared needles,
hemodialysis, and needle sticks (or other wounds caused by sharp
implements) in healthcare workers.

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HBV
• Transmission: Perinatal, sexual, parenteral, healthcare, sporadic
• Perinatal: intrapartum/in utero, +/- breast milk. Neonates usually
asymptomatic.
• Sexual: faster than HIV/HCV. Vaginal/genital-rectal/oral-genital
intercourse
• Parenteral: hemophiliacs, those on renal dialysis, organ transplant
recipients
• Healthcare: needlestick/other accidents
• Sporadic: unknown cause. Likely sexual or blood contact

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HBV
• HBsAg: first serum marker seen in acute infection.
• Represents the presence of hepatitis B virus (HBV) virions (Dane
particles) in the blood.
• HBeAg: marker of viral replication, also present. When viral replication
slows, HBeAg disappears, and antibody to HBeAg (anti-HBe) is
detected and may persist for years.

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HBV
• The first antibody to appear: antibody to hepatitis B core antigen
(HBcAg) (anti-HBc).
• Initially IgM class: (the presence of IgM anti-HBc is diagnostic for
acute HBV infection.)
• Weeks later, IgM anti-HBc disappears, and IgG anti-HBc is detected
• HBsAg may remain detectable for life in many patients.
• Individuals who have positive findings for HBsAg are termed carriers
of HBV. - They may be inactive carriers or they may have chronic
hepatitis.

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HBV vaccine
• The HBV vaccine delivers recombinant HBsAg to the patient without
HBV DNA or other HBV-associated proteins.
• > 90% of recipients develop protective anti-HBs.
• Vaccine recipients are not positive for anti-HBc unless they were
previously infected with HBV.

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HEP C
• Flaviviridae family
• Commonest cause of chronic viral hepatitis
• Can be transmitted parenterally, perinatally, and sexually.
• Transmission occurs by percutaneous exposure to infected blood and
plasma.
• Transmitted most reliably through transfusion of infected blood or
blood products, transplantation of organs from infected donors, and
sharing of contaminated needles among IV drug users.
• Chronic Hep C infection – liver cirrhosis, liver cancer
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HEP D
• Single species in the Deltavirus genus
• Single-stranded RNA
• The viral particle is 36 nm in diameter, contains hepatitis D antigen
(HDAg) and the RNA strand.
• Uses HBsAg as its envelope protein; HBV coinfection is necessary for
the packaging and release of HDV virions from infected hepatocytes.
• Modes of transmission for HDV are similar to those for HBV
• Perinatal transmission is rare.

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HEP E
• Single species in the Hepevirus genus
• Single-stranded RNA virus
• Transmitted primarily via the fecal-oral route
• Fecally contaminated water providing the most common means of
transmission.
• Person-to-person transmission is rare, though maternal-neonatal
transmission does occur.
• Frequently self-limiting

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HEP G
• Also known as human pegivirus [HPgV])
• Similar to viruses in the Flaviviridae family, which includes HCV.
• RNA virus
• Transmitted through blood and blood products.
• HGV coinfection is observed in 6% of chronic HBV infections and in 10%
of chronic HCV infections
• About 75% of HPgV infections clear within 2 years of infection, and 25%
persist.
• HGV is associated with acute and chronic liver disease, but it has not
been clearly implicated as an etiologic agent of hepatitis.
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PREVENTION
• Vaccination: HAV, HBV & HDV but not HCV or HEV
• Screen close contacts of pts (spouses, children)
• Improved sanitation, strict personal hygiene, and hand washing (HAV)
• Travelers to endemic areas should not drink untreated water or ingest raw seafood
or shellfish.
• Fruits and vegetables should not be eaten unless they are cooked or can be peeled.
• PEP with HAIG, HBIG
• Screen pregnant mothers for HBV, tx depending on mother’s viral load & HIV
coinfection (start tx in 3rd trimester)
• Vaccination of neonate born to infected mother within 12h of birth (Birth dose),
then ct routine vaccination. (Total: 4 doses)
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PEP for Hep B
Recommendations for PEP for pple exposed to HBsAg+ individuals:
• Perinatal exposure – HBIG (to neutralize ags that might have crossed thru placenta) plus
HBV vaccine at birth (90% effective)
• Sexual contact with an acutely infected patient – HBIG plus HBV vaccine
• Sexual contact with a chronic carrier – HBV vaccine
• Household contact with an acutely infected patient – None
• Household contact with an acutely infected person resulting in known exposure – HBIG,
with or without HBV vaccine
• Infant (age < 12 months) primarily cared for by an acutely infected patient – HBIG, with
or without HBV vaccine
• Inadvertent percutaneous or permucosal exposure – screen first, give HBIG if screen is
neg, HBV vaccine(if they hadn’t been vaccinated)
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EBOLA VIRUSES
• Ebola virus is named from a river in Zaire that was the site of an outbreak of hemorrhagic
fever in 1976.
• The disease begins with fever, headache, vomiting, and diarrhea.
• Later, bleeding into the gastrointestinal tract occurs, followed by shock and disseminated
intravascular coagulation.
• The hemorrhages are caused by severe thrombocytopenia. The mortality rate associated with
this virus approaches 100%.
• Is a filo virus of the family of filo viridae.
• It is an RNA and enveloped with a characteristic of filamental structure.
• It has four known strain or species: Zaire, Sudan, Reston and ivory cost.
• Transmission is contact from person to person or any organ of the infected person . Injuries
with needle or handling body fluids without protection, handling of dead bodies of suspected
victim should be discouraged.
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Yellow fever
• Yellow fever virus, an enveloped RNA virus, 40–50 nm in width, of
family Flaviviridae
• symptoms include fever, chills, loss of appetite, nausea, muscle pains
and headaches.
• Dx: clinical, serology
• spread to people by the bite of an infected (Aedes) mosquito.
• Prevention: vaccination and avoidance of mosquito bites in areas
where yellow fever is endemic, vector control

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Rabies
• A viral disease that causes inflammation of the brain in humans and
other mammals.
• Symptoms: fever and tingling at the site of exposure. Later followed
by one or more of: nausea, vomiting, violent movements,
uncontrolled excitement, an inability to move parts of the body,
confusion, and loss of consciousness.
• Rabies is caused by rabies virus species; Lyssavirus genus, in the family
Rhabdoviridae. Enveloped, ss RNA
• Prevention: rabies vaccine and rabies immunoglobulin for people who
have been exposed to rabies
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Monkeypox
• Monkey pox virus is a viral zoonosis
• Cases confirmed in Europe and into North America, May 2022
• Symptoms very similar to those seen in the past in smallpox but milder
& include headache, skin rash, fever, body aches, chills, swollen lymph
nodes, and exhaustion.
• Incubation period, can range from five to 21 days.
• The illness typically resolves within two to four weeks.
• Transmission - close skin contact, air droplets, bodily fluids, and virus-
contaminated objects.
• Vaccines for monkeypox have been approved for limited circulation.
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Tumor viruses
• Viruses are etiologic factors in the development of several types of
human tumors, including two of great significance worldwide—
cervical cancer and liver cancer.
• At least 15% of all human tumors worldwide have a viral cause.
• Viruses can cause benign or malignant tumors.

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Baltimore classification of viruses

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 REFERENCES
• Sherri’s Medical Microbiology 7th edition
• Jawetz, Melnick & Adelberg's Medical Microbiology. New York;
London: McGraw-Hill 24th edition
• John B. Carter and Venetia A. Saunders - Virology Principles And
Applications, 2007

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 THANK YOU!

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