1. Picornaviridae (rhinovirus, coxsackie virus, echovirus, enterovirus) 2. Coronaviridae (coronavirus, SARS-CoV) 3. Orthomyxoviridae (Influenza A,B,C virus) 4. Paramyxoviridae (Parainfluenza virus, respiratory synctial virus, metapneumovirus, measles virus)

Minor changes in either the hemagglutinin or neuramidase, or both Minor antigenic variations reslut from mutations in hemagglutinin and neuraminidase genes The hemagglutinin mutations are primarily found in the four antibody combining sites in the hemagglutinin protein

Clinical signs and epidemiology Lab diagnosis Rapid antigen capture detects nucleoprotein (15 min) rt-PCR Hemagglutination/ Serology Virus isolation Immunofluorescent techniques

Respiratory Viruses Flashcards by Victor Redmon

Respiratory Viruses

Influenza virus

Rhinovirus

Coronavirus

Parainfluenza virus

Respiratory synctial virus

Metapneumovirus

Adenovirus (sometimes)

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Virus families

Picornaviridae (rhinovirus, coxsackie virus, echovirus, enterovirus)
Coronaviridae (coronavirus, SARS-CoV)
Orthomyxoviridae (Influenza A,B,C virus)
Paramyxoviridae (Parainfluenza virus, respiratory synctial virus, metapneumovirus, measles virus)

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Orthomyxovirus

Family:

Genus:

Individual Strain:

Subtypes:

Types:

Family: Orthomyxovirus

Genus: Influenza; Thogotovirus

Individual Strain: A/BAngkok/1/79(H3N2)

Subtypes: Based on hemagglutinin and neuramidase

Types: Based on matrix and nucleoprotein antigens

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Antigenic Drift

Minor changes in either the hemagglutinin or neuramidase, or both

Minor antigenic variations reslut from mutations in hemagglutinin and neuraminidase genes
The hemagglutinin mutations are primarily found in the four antibody combining sites in the hemagglutinin protein

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Major antigenic shift

Occurs infrequently, either hemagglutinin alone or neuraminidase as well. Occurs as a result of gene reassortment between a human and animal strain

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Influenza Pathogenesis

Influenza is an acute respiratory disease
infects ciliated epithelial cells lining the upper respiratory tract, trachea, bronchi
Virus replication - destruciton of respiratory epithelium
Cell damage also due to virus activated CTL
Viremia - not a major role

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Acute influenza infection in adults - symptoms

Rapid onset of fever, malaise, myalgia sore throat and nonproductive cough

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Acute influenza infection in children

Acute disease similar to that in adults but with higher fever, GI tract symptoms, otitis media, myositis

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Complications of influenza virus infection

Primary viral pneumonia

Secondary bacterial pneumonia

Myositis and cardiac involvement

Neurologic syndromes

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Influenza diagnosis

Clinical signs and epidemiology
Lab diagnosis
- Rapid antigen capture detects nucleoprotein (15 min)
- rt-PCR
- Hemagglutination/ Serology
- Virus isolation
- Immunofluorescent techniques

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Replication and Spread of influenza (7 steps)

Binding
Coating/Fusing
Transcription
Proteins synthesized
Replication
Assembly
Budding

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What is the influenza virus cellular receptor?

Sialic acid

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How does the viral membrane fuse with the vesicular membrane inside the cell?

Lowers the pH which triggers fusion and release of contents

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Prevention and control of influenza: Immunization

Formalin inactivated - mixture of prevalent antigenic types
Attenuated infectious viruses - intranasal administration
Experimental - DNA vaccines - reverse transcriptase

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Prevention and control of influenza: Chemotherapy

Amantadine and rimantadine - inhibit uncoating by blocking M2 protein
Ribavirin - inhibits syntehsis of viral RNA
Zanamivir and Oseltamivir (Tamiflu) neuraminidase inhibitors

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Influenza is usually treated with a _______ vaccine

Trivalent

Rhinovirus (characteristics)

Causes 50% of common colds
>150 serotypes identified
Temperature sensitive - grows better at 33º than 37º
Secretory IgA is most important in limiting reinfection
Transmission by respiratory secretions

Rhinovirus symptoms

Headache
Cough
Sore throat
Mucus
Nasal discharge

All due to inflammatory response

Rhinovirus prevention and control

No effective prevention and control measures to date

Experimental
- Viral protease inhibitors (Ruprintrivir)
- WIN compounds - block uncoating by inserting in virus surface pore

Rhinoviruses are transmitted via _______

fomites

Coronaviruses (characteristics)

Cause common colds - watery eyes, sneezing, nasal congestion, sore throat

Disesae limited to upper respiratory tract, infects epithelial cells

No vaccine available

Coronavirus Outbreaks

2002-2003: SARS outbreak caused by SARS-CoV
2012 - acute pneumonia and renal failure MERS-CoV originally named hCoV EMC

Coronavirus - SARS

Fatality Rate:

Transmission:

Source:

Vaccines:

Sudden acute respiratory syndrome

Fatality Rate: 10%

Transmission: Mainly by face-to-face contact; virus in respiratory secretions and feces; not highly contagious

Source: Bats, and other animals sold in markets in China

Vaccines: none currently available

MERS-CoV

Difference from SARS:

First Reported:

Origin:

Cases to date:

Middle East Respiratory Syndrome

Difference from SARS:

Uses a different cellular receptor
Does not readily pass from person to person

First Reported: September 2012 (May 2014-US)

Origin: Middle East (nosocomial infections documented)

Cases to date: 400

Paramyxoviridae Family

Morbillivirus Paramyxovirus Pneumovirus Heniparvirus

Paramyxovirus family virus proteins

F: fusion protein HN: Hemagglutinin virus attachment Neuraminidase virus release NS1 and NS2: Nonstructural proteins that modulate the immune response important in vivo

Paramyxoviruses replicate in the \_\_\_\_\_\_

cytoplasm

Human Parainfluenza Viruses (HPIV) - key issues

* Common cause of acute and lower respiratory illness in infants/young children/elderly/immunocompromised * Common cause of croup * Different types (HPIV1, HPIV2, HPIV3, HPIV4) * Reverse genetics systems for HPIVs have helped attenuating mutations and to incrementally attenuate * Vaccines have entered pediatric trials in Phase 1

Paramyxoviridae - Respiratory Synctial virus (RSV)

* Most common cause of fatal acute respiratory tract infection in infants and young children * Infects virtually everyone by age 2 * Re-infections occur throughout life, can be severe in elderly

Disease mechanisms of Respiratory Syncytial Virus

* Pneumonia results from cytopathologic spread of virus (including syncytia) * Bronchiolitis is most likely mediated by host's immune response * Narrow airways of young infants are readily obstructed by virus-induced pathologic effects * Maternal antibody does not protect infant from infection

RSV - pathogenesis

Typical giant cells - pink intracytoplasmic inclusions

Immune response in infants vs adults to RSV

* Infants * TH2 response * Mast cell activation * Eosinophila * Wheezing * Adults * Th1 response - IFN * Macrophages, NK cells, Cell mediated immunity * B cells * Cytolysis * Antiviral cytokines * Virus clearance

RSV treatment prevention and control ## Footnote Otherwise healthy infant: Premature or immunocompromised infants: Premature infants: Vaccine:

Otherwise healthy infant: treatment is supportive, oxygen, IV fluids, nebulized cold steam Premature or immunocompromised infants: Aerosolized ribarin Premature infants: Passive immunization with anti-RSV Ig and humanized monoclonal antibodies against viral fusion protein Vaccine: No vaccine currently available

Human Metapneumovirus - hMPV (Characteristics)

First identified in 2001 Clinical spectrum of disease similar to RSV - most severe in infants, elderly, immunocompromised, those with COPD Second most common cause of lower RTI in young children By 5 years of age all children are seropositive

hMPV treatment and prevention

* Most treatment is supportive * Ribavirin - inhibitory activity against hMPV * Immunoglobulins * IVIG * Humanized monoclonals * Ribavirin + IVIG

Paramyxoviridae - Hendra and Nipah Virus

Two emerging respiratory viruses with high mortality rates Have made the apparent jump from bats to people in Australia and Asia

Adenovirus (Characteristics)

* \>50 human types identified * Cause a wide spectrum of disease including respiratory infection * Conjunctivitis * GI infections * Hemorrhagic cystitis * In respiratory tract, can cause destructive productive infection, persistent infection with virus shedding, or latent infections

In addition to previously mentioned groups, ______ \_\_\_\_\_\_ are also highly susceptible to adenoviruses

military recruits