RNA Nonenveloped Viruses

PICORNAVIRUSES CALICIVIRUSES REOVIRUSES

1- PICORNAVIRUSES

small (20-30 nm) nonenveloped, icosahedral, +ve ssRNA viruses Replicate in the cytoplasm resist lipid solvents (e.g. ether) The family includes 2 groups: 1- Enteroviruses 2- Rhinoviruses

 Genera of Picornaviruses Genera that infect humans Enterovirus Diseases of the Polio human (and other) Coxsackie A and B alimentary tract Echo (e.g. polio virus) Other enteroviruses Rhinovirus Disease of the nasopharyngeal region (e.g. common cold virus)

Properties of Rhino- and Enteroviruses

pH Optimu Deterge Serotyp Transmi Site of sensitivity m nt es ssion primary growth sensitivi infection tempera ty ture

Rhino labile to viruse acid pH s

33 degrees C (approx )

>100

aerosol upper respirat ory tract

Enteroresistant 37 Resistan 72 viruse to acid pH degrees t s C (approx )

orofecal

gut

ENTEROVIRUSES
Enteroviruses Virus family Serotypes Polio 1-3 Coxsackie A 1 - 22, 24 Coxsackie B 1-6 Echovirus 1 - 9, 11 - 27, 29 34 Hepatitis A Enterovirus 72

Poliovirus

Important Properties:
- Infection is limited to the primates (receptor?) - Three serologic types are present - CD155, the polio virus receptor, is expressed (in spinal
cord anterior horn cells, dorsal root ganglia, skeletal muscle, motor neurons and some cells of the lymphoid system)

- For unknown reasons, polio virus does not spread to the cells of the central nervous system in all patients

Replication Cycle

Interaction of the virus with its receptor Enters the cell, uncoating The genome RNA functions as mRNA Translated into one very large polypeptide viral RNA polymerase synthesized the progeny RNA genomes Replication (+ve ssRNA::-ve ssRNA:: +ve ssRNA) Assembly occurs at the cytoplasm Release occurs by lysis of the cells

Transmission & Epidemiology

Poliovirus is spread via the fecal-oral route Most disease results from type 1 polio virus Poliovirus caused about 21, 000 cases of paralytic poliomyelitis in the United States each year in the 1940's - 50's Today, the number of cases of paralytic polio in the US is fewer than 10 and these are the result of the attenuated (Sabin) vaccine reverting to virulence

Pathogenesis & Immunity

Replicate 1st in oropharynx & GI Then, spread via blood to the CNS The virus replicates in the motor neurons located in the anterior horn of the spinal cord

Paralysis occurs due to the death of these cells Immunity is lifelong type-specific

Clinical Findings

Asymptomatic polio infection:

- This occurs when the replication of the virus is restricted to the GI tract - IP is 10-14 days

Abortive poliomyelitis (minor illness):

- is febrile disease and occurs in the first week of infection - occurs in about 5% of infected individuals - general malaise which may be accompanied by vomiting, a headache and sore throat

Clinical Findings Cont.

Non-paralytic poliomyelitis:
stiff neck
- This is similar to aseptic meningitis with fever, headache & a

Paralytic polio:
- flaccid paralysis is the predominant finding - Respiratory paralysis can occurs due to brain stem involvment

Post-polio

syndrome:

- Occurs many years after the acute illness - involves further loss of function in affected muscles perhaps as a result of further neuron loss.

Laboratory Diagnosis

Isolation of the virus Detection a rise in antibody titer Clinical spicemens include: throat swabs, stool or spinal fluid

Treatment & Prevention

No antiviral therapy

Prevented by vaccination using: 1- killed vaccine (Salk vaccine, inactivated vaccine, IPV) 2- live attenuated vaccine (Sabin vaccine, oral vaccine, OPV) (current version of IPV is called enhanced polio vaccine eIPV)

Coxsackieviruses

There are many infections caused by Coxsackie viruses, most of which are never diagnosed precisely Coxsackie type A usually is associated with surface rashes (exanthems) Type B typically causes internal symptoms (pleurodynia, myocarditis) Both can also cause paralytic disease or mild respiratory tract infection.

Coxsackieviruses
Meningitis:

- Enteroviruses are the major cause of viral meningitis - Both Coxsackie virus A and B can cause aseptic meningitis - Viral meningitis typically involves a headache, stiff neck, fever and general malaise - Most patients recover from the disease unless encephalitis occurs
- The disease is most prevalent in the summer and fall

Coxsackieviruses

Herpangina:
- Coxsackie virus A can cause a fever with painful ulcers on the palate and tongue leading to problems swallowing and vomiting - Treatment of the symptoms is all that is required as the disease subsides in a few days.

Coxsackieviruses

Hand, foot and mouth disease: (HFMD)

- This is an exanthem (rash) caused by Coxsackie type A16 - Symptoms include fever and blisters on the hands, palate and feet. - it subsides in a few days

Myocarditis:
- Type A and B can cause myocarditis in neonates and young children - Fever, chest pains, arrhythmia and even cardiac failure can result - Mortality rates are high.

Echoviruses

ECHO = enteric cytopathic human orphan Cause aseptic meningitis, URT, febrile illness, infantile diarrhea & hemorrhagic conjunctivitis

Transmitted by fecal-oral route Diagnosed by isolation in cell culture No vaccine or antiviral available

Other enterovirus diseases

Acute hemorrhagic conjunctivitis is caused by Coxsackie A24 and Enterovirus 70. The disease resolves in a week or two Enterovirus 71 is one of the leading causes of viral CNS disease, including meningitis, encephalitis, & paralysis Enterovirus 72 is hepatitis A virus

RHINOVIRUSES
Rhinoviruses

common cold

are the main cause of the

There are more than 100 serotypes They are sensitive to low pH and replicate well at 33 C Infect the URT & spread directly via aerosols or by fomites such as hands and other forms of direct contact

RHINOVIRUS DISEASE

There are nearly 62 million cases of the common cold annually in the US million of these cases affect Americans under age 17 are nearly 22 million school-loss days annually due to the common cold are approximately 45 million bed days annually associated with the common cold

52.2

There

There

Clinical Findings

IP is 2-4 days Symptoms include discharging or blocked nasal passages often accompanied by sneezes, and perhaps a sore throat The illness lasts about 1 week viruses cause symptoms that are similar to those of rhinoviruses
(parainfluenzaviruses, coronaviruses and enteroviruses)

other

Treatment & Prevention

There is usually no need to treat the infection But rehydration and keeping the airways

unblocked is advisable

Prescription of aspirin to relive fever ?? Interferon nasal sprays have little effect The best way to avoid spreading the virus is interrupt the infection chain by hand washing

2- CALICIVIRUSES

They are almost like Picornaviruses differ in having: 1- larger genome 2- having distinctive spikes on the surface human pathogens in this family: 1- Norwalk virus (norovirus) 2- Hepatitis E virus

But

Two

Norwalk virus (Norovirus)

One of the most common causes of viral gastroenteritis in adults

It is named after an outbreak (Ohio, 1969) It has +ve ssRNA, nonenveloped, icosahedral

Uncertain serotypes Replicative cycle is unclear but similar to Picornaviruses

Transmission & Epidemiology

Fecal-oral (seafood & water) Person-to-person (group settings) Outbreaks in cruise ships, schools, camps Low infectious dose, resistance to chlorination & drying, are factors enhancing the infection

Pathogenesis & Immunity

Infection is limited to the mucosal cells of GI Watery diarrhea W/O blood Mostly asymptomatic Short immunity (reinfection)

Clinical Findings

Sudden onset of vomiting & diarrhea With low-grade fever & abdominal cramps

But W/O blood It lasts for several days

Treatment & Prevention

Diagnosed clinically and rarly by PCR No antiviral drugs or vaccine But IV fluid may required Personal hygiene

3- REOVIRUSES

REO = Respiratory Enteric Orphan

Rotaviruses is the most important human pathogen in this family The most common cause of viral gastroenteritis in young children

Important Properties

Segmented dsRNA, 2-layer icosahedral Contains RNA-dependent RNA polymerase

Infect many domestic animals (human?) Six human serotypes

Replication

Attachment (-adrenergic receptor) Entry Synthesis of mRNA (10-11 segments) Translation to structural & nonstructural proteins RNA-polymerase synthesizes strand, then the +strand synthesize

Released by lysis

Transmission & Epidemiology

Fecal-oral route

Pathogenesis & Immunity

- Replication in mucosal cells of small intestine cause excess secretions of fluids & electrolytes - No inflammation, no bloody diarrhea - IgA is protective (serospecific)

Laboratory Diagnosis

RIA or ELISA (stool) Immunoelectron microscopy 4-fold increase in Abs titer

Treatment & Prevention

No antivral therapy, no vaccine Hygienic measures like: - proper sewage disposal - hand washing are helpful