s l 2013 RNA VIRUSES 1 Virus Characteristics Epidemiology Pathogenesis and Virulence Diseases Lab Diagnosis Treatment

Enterovirus (Picornaviridae)

Icosahedral Non-enveloped SS+ non-

segmented Stable at low pH of

stomach

Spread: contaminated food/water

Location: stomach and GIT

Risk Factors: 1. Summer

At Risk: 1. Neonates (coxsackie, enterovirus) 2. Children and adults (poliovirus)

Pathogenesis 1. Can replicate in various tissues

(tropism) 2. Binds to specific receptors on host cell

surface 3. Viremia: via blood/lymphatics Virulence 1. Cytolytic 2. Shed in feces for long period Clearance 1. Antibodies and interferon (secreted by TH1 cells)

Poliovirus 1. Asymptomatic Illness (90%) 2. Abortive Poliomyelitis (5%): fever, headache, malaise, pharyngitis

3. Non-paralytic Poliomyelitis or Aseptic Meningitis: virus progresses to CNS and meninges

4. Paralytic Polio: virus spreads to anterior horn of SC and motor cortex of brain; spinal paralysis; usually permanent

5. Postpoliomyelitis syndrome: 20-30% of patients who recover from PP experience muscle weakness, atrophy 25-35 years after the illness

Coxsackie A 1. Herpangina: fever, sore throat; ulceration in mouth and uvula

2. Hand-foot-mouth Disease Coxsackie B 1. Myocardial and Pericardial Infections: sudden, unexplained onset of heart failure; high mortality

2. Pleurodynia (Bornholm Disease, Devils Grip): unilateral, acute, excruciating chest pain; vomiting

Echovirus 1. Viral Meningitis: most common viral cause; milder than bacterial; CSF: increased lymphocytes, normal glucose levels

Culture Serology PCR Meningitis: CSF cytology (inc lymphocytes, normal glucose)

Pleconaril Salk Killed Polio

Vaccine: IgG Sabin Live

Attenuated Vaccine: IgG and IgA

Rhinovirus (Picornaviridae)

Icosahedral Non-enveloped SS+ non-

segmented Acid Labile Require lower

temperatures

Spread: respiratory, hand to hand contact

Location: URT

1. Optimal temperature is 33C for growth (nasal passages) 2. 100 different serotypes: difficult to establish a protective mechanism

Common Cold: mild cough, pharyngitis, malaise, myalgia, low-grade fever; self-limiting

Usually not required

Self-limiting No vaccine

Norovirus (Caliciviridae)

Icosahedral Non-enveloped SS+ non-

segmented

Spread: persons Location: GIT Risk Factors:

1. Schools, camps, prisons, cruises 2. Oysters

At Risk: 1. Adults

1. GIT replication and shed in the stool 2. Inhibits intestinal brush border function 3. Improper absorption of nutrients and water

Adult Gastroenteritis: major viral cause in adults; nausea, vomiting, watery diarrhea, self-limiting

PCR: gold standard

ELISA: viral Ab

Bismuth salicylate: reduce symptoms

s l 2013 RNA VIRUSES 2 Rotavirus (Reoviridae)

Icosahedral Enveloped Double stranded Segmented

Spread: feco-oral and respiratory

Location: GIT Risk Factors:

1. Jan-Mar At Risk:

1. Infants

1. Initial infection through small intestine epithelia 2. Toxin-like action: virus causes atrophy and shortening of villi 3. Decrease reabsorption of sugars and water diarrhea

Infantile Gastroenteritis: most common cause in infants; mild to severe watery, non-bloody diarrhea with loss of electrolytes

Serology Electron microscopy

Ganciclovir Foscarnet Screening

reduces intrauterine transmission

Measles Virus (Paramyxoviridae)

Helical SS- non-segmented One serotype

Spread: respiratory Location: RT Risk Factors:

1. Unimmunized

1. Initial infection in RT; attaches to CD46 via Hemaggluitinin (HA); F (fusion) protein facilitates uptake of virion 2. Replication in respiratory epithelia 3. Viremia: spread to LN, conjunctiva, RT, urinary tract, blood vessels, CNS 4. CMI controls infection *No neuraminidase (NA)

Measles: 1. Fever, cough, coryza and conjunctivitis 2. Koplik spots: small white spots on bright red mucous membrane on throat

3. Generalized macular rash: from head to lower extremities; patient is no longer infectious

Atypical Measles 1. Occur in people with older, inactivated vaccine 2. More intense rash Complications 1. Otitis media, secondary bacterial infection, pneumonia 2. Giant cell pneumonia: T-cell deficient patients 3. Postinfectious encephalitis: rare (1/1000); autoimmune vs. myelin basic protein 4. Subacute sclerosing panencephalitis: rare, slow viral infection with CNS manifestations

Visual diagnosis (Koplik spots)

Live, attenuated vaccine (MMR)

Mumps Virus (Paramyxoviridae)

Helical SS- non-segmented One serotype

Spread: respiratory Location: RT Risk Factors:

1. Unimmunized

1. Initially infects RT; local replication 2. Viremia: infects parotid gland

1. Parotiditis: infection and swelling of salivary glands (primarily parotid); inflamed ostium of Stensens duct

2. Orchitis/Oophritis: testicular inflammation; may cause sterility

3. Aseptic Meningitis and Encephalitis: rare

4. Pancreatitis

Virus recovered from saliva, urine

Multi-nucleated giant cells

ELISA IF Hemagglutinin inhibition

MMR vaccine

Parainfluenza Virus

(Paramyxoviridae)

Helical SS- non-segmented No viremia Limited to RT Common infection

Spread: respiratory, person-person

Location: RT only Risk Factors:

1. Nosocomial At Risk:

1. Infants

1. Only infects the respiratory tract 2. Does not cause viremia 3. Hemagglutinin and neuraminidase activity 4. Short protective immunity

1. Croup (serotype 1&2): seal bark cough; subglottal swelling; laryngotracheobronchitis

2. Bronchitis and pneumonia (serotype 3): common in infants and elderly

3. Cold-like upper RTI (serotype 4): treat with nebulized air

Unnecessary Nebulized air

s l 2013 RNA VIRUSES 3 Respiratory

Syncytial Virus (Paramyxoviridae)

Helical SS- non-segmented

Spread: respiratory Location: URT and

LRT Risk Factors:

1. Nosocomial At Risk:

1. Infants

1. HA and F protein facilitates attachment and entry into respiratory epithelia 2. Cell-cell spread of virus 3. No antibody protection: maternal Ab and natural infection do not protect from virus

1. Common cold with rhinorrhea (URT): adults

2. Bronchiolitis (LRT): most important viral cause in infants

Culture RT-PCR ELISA

Ribavarin No vaccine

Influenza Virus (Orthomyxoviridae)

Helical SS- segmented

Spread: respiratory Location: respiratory

tract Risk Factors:

1. Seasonal: Oct to May

At Risk: 1. Infants and elderly 2. Adults: classic flu 3. Seronegative individuals 4. Immunocomp: high risk

**Currently, H7N9 is

a pandemic (human and avian flu strains)

Pathogenesis 1. Hemagglutinin (HA) facilitates attachment by binding to sialic acid 2. P proteins cleave cap from host mRNA for capping of viral mRNA 3. RNA-dep RNA pol: facilitate synthesis of progeny mRNA from pre-existing viral mRNA 4. Infects URT then LRT (descending infection 5. Cause damage to respiratory epithelia 6. IFN, NK and T cells facilitate immune resolution 7. Neuraminidase (NA) facilitates viral release and spread from infected cell 8. Could lead to influenza, primary viral pneumonia, secondary bacterial infection or post-infectious encephalitis Virulence 1. Antigenic Drift: mutation in genes encoding HA or NA; error prone RNA-dependent RNA polymerase; both influenza A & B exhibit this 2. Antigenic Shift: reassortment of genomic segments (H1N1 to H3N2); causes pandemic due to novelty and lack of immunity; only influenza A *Antigenic shift occurs due to reassortment of influenza A viruses in different species (swine, avian, horses)

Influenza 1. Classic: malaise, headache, myalgia, high fever, non-productive cough

2. Asymptomatic to severe depending on existing immunity and circulating strain

3. Children: high fever, croup, otitis media

4. Usually self-limiting 5. Complications in immunocompromised: a. Primary viral pneumonia b. Secondary bacterial infection c. Post-infectious encephalitis d. Guillen-Barre Syndrome e. Myositis f. Reyes syndrome: aspirin-associated

Culture Hemadsorption ELISA Serology RT-PCR

Amantadine & rimantadine (M2 protein)

Zanamivir & Oseltamivir (NA protein)

Vaccine (formalin-inactivated): contains common subtypes of virus currently in circulation

Coronavirus (Coronaviridae)

Helical SS+ non-

segmented

Spread: respiratory Location: respiratory

tract, GIT Risk Factors:

1. H/O exposure to place with coronavirus

1. Transmitted in respiratory droplets from bodily fluids 2. Establish infection in RT and GIT **MERS: Middle East Respiratory Syndrome

SARS (Severe Acute Respiratory Syndrome)

1. Outbreak in South China and spread throughout the world

2. Atypical Pneumonia: high fever, chills, rigors, headache, dizziness, cough

3. Gastroenteritis: present in 20% of patients (adults or children)

Serology PCR

No treatment

s l 2013 RNA VIRUSES 4 Rabies Virus (Rhabdoviridae)

Helical SS- non-segmented Neurotropic Bullet-shaped

Spread: saliva from animal

Location: peripheral nerves

Risk Factors: 1. Unvaccinated animals 2. Bats, raccoons, skunks

At Risk: 1. Vets and animal handlers 2. Person bitten by rabid animal 3. Inhabitants of countries with no pet vacc.

Pathogenesis 1. Bite of an animal transfers saliva to human victim. 2. Ascending infection via peripheral nerves to brain 3. Massive viral replication in the brain 4. Descending infection to salivary glands, cornea, skin and muscles

Rabies Stages: 1. Incubation: 60-365 days after bite (depends on location); asymptomatic

2. Prodrome: fever, nausea, vomiting, lethargy; pain on site of bite; virus reaches CNS and multiplies; 2-10 days

3. Neurologic: hydrophobia (severe pain upon drinking); pharyngeal spasms, anxiety, hyperactivity, depression; CNS symptoms arise: confusion, delirium, paralysis; 2-7 days

4. Coma: cardiac arrest, hypotension, hypoventilation

5. Death

Negri bodies!! DFA: viral Ag RT-PCR ELISA

Post-exposure prophylaxis: virus travels slow

Immediate wound cleansing: KMNO4 and antiseptics

Active and passive immunization

Alphavirus (Togaviridae)

Helical SS+ non-

segmented Arbovirus

(arthropod-borne)

Spread: mosquito bite (Culex)

1. Mosquito bite introduces virus to human. 2. Viremia: spread to target organs

1. Acute Encephalitis: Eastern and Western equine encephalitis v.

2. Acute arthropathy: Chikungunya v. 3. Febrile illness: Venezuelan equine encephalitis v.

WEE, EEE, VEE

Rise in Ab titers

Control of mosquito population

Rubella Virus (Togaviridae)

Helical SS+ non-

segmented Congenital Disease One serotype

Spread: respiratory Location: RT Risk Factors:

1. Unvaccinated 2. Crowded conditions

At Risk: 1. Children 2. Adults 3. Neonates

1. Respiratory secretions of an infected person is the only mode of transmission 2. Viremia: spread from lungs to liver, spleen, LN 3. No cytopathic effect 4. CMI limits infection; Ab helps

1. German Measles: descending maculopapular rash that starts from the face; occipital lymphadenopathy; more severe in adults with arthritis 2. Congenital Rubella Syndrome: virus replicates in placenta and spread to fetal blood; teratogenic effect; depending on tropism and stage of development; cataracts, deafness, hepatitis, CHD and CNS deficits

RT-PCR Serology Blueberry muffin baby

MMR vaccine No treatment

Flavivirus (Flaviviridae)

Helical SS+ non-

segmented Arbovirus Over 60 serotypes

Spread: mosquito or tick bite (Aedes or Culex)

Location: macrophages

Pathogenesis 1. Mosquito bite introduces virus to human. 2. Viremia: spread to target organs Virulence 1. Cytolytic 2. Non-neutralizing Ab: can enhance infection via Fc receptors on macrophages by stimulating phagocytosis activation of memory T cells

1. Dengue Fever: breakbone fever; transmitted by Aedes mosquito; high fever, headache, rash, back and bone pain 2. Dengue Shock syndrome & Dengue Hemorrhagic fever: occur on rechallenge by other dengue fever strains 3. Encephalitis: SLE, WNV, JE

Mosquito cell line

RT-PCR ELISA

Control of mosquito population

Other Medically Important RNA Viruses Human Metapneumovirus RSV-like; cause bronchiolitis Nipah and Hendra virus fruit bat reservoir; flu-like symptoms, possible complications with seizures and coma Filoviridae Ebola/Marburg hemorrhagic fever often fatal! Bunyavirus (Hantavirus) hemorrhagic fever; Hantavirus Respiratory Syndrome: death within 10 days Arenavirus lymphocytic choriomeningitis virus; Lassa fever encephalitis