Respiratory Viruses

Question 1

Respiratory Viruses

Answer 1

Influenza virus

Rhinovirus

Coronavirus

Parainfluenza virus

Respiratory synctial virus

Metapneumovirus

Adenovirus (sometimes)

Question 2

Virus families

Answer 2

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)

Question 3

Orthomyxovirus

Family:

Genus:

Individual Strain:

Subtypes:

Types:

Answer 3

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

Question 4

Antigenic Drift

Answer 4

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

Question 5

Major antigenic shift

Answer 5

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

Question 6

Influenza Pathogenesis

Answer 6

• 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

Question 7

Acute influenza infection in adults - symptoms

Answer 7

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

Question 8

Acute influenza infection in children

Answer 8

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

Question 9

Complications of influenza virus infection

Answer 9

Primary viral pneumonia

Secondary bacterial pneumonia

Myositis and cardiac involvement

Neurologic syndromes

Question 10

Influenza diagnosis

Answer 10

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

Question 11

Replication and Spread of influenza (7 steps)

Answer 11

1. Binding
2. Coating/Fusing
3. Transcription
4. Proteins synthesized
5. Replication
6. Assembly
7. Budding

Question 12

What is the influenza virus cellular receptor?

Answer 12

Sialic acid

Question 13

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

Answer 13

Lowers the pH which triggers fusion and release of contents

Question 14

Prevention and control of influenza: Immunization

Answer 14

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

Question 15

Prevention and control of influenza: Chemotherapy

Answer 15

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

Question 16

Influenza is usually treated with a _______ vaccine

Answer 16

Trivalent

Question 17

Rhinovirus (characteristics)

Answer 17

• 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

Question 18

Rhinovirus symptoms

Answer 18

• Headache
• Cough
• Sore throat
• Mucus
• Nasal discharge

All due to inflammatory response

Question 19

Rhinovirus prevention and control

Answer 19

No effective prevention and control measures to date

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

Question 20

Rhinoviruses are transmitted via _______

Answer 20

fomites

Question 21

Coronaviruses (characteristics)

Answer 21

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

Disesae limited to upper respiratory tract, infects epithelial cells

No vaccine available

Question 22

Coronavirus Outbreaks

Answer 22

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

Question 23

Coronavirus - SARS

Fatality Rate:

Transmission:

Source:

Vaccines:

Answer 23

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

Question 24

MERS-CoV

Difference from SARS:

First Reported:

Origin:

Cases to date:

Answer 24

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

Question 25

Paramyxoviridae Family

Answer 25

Morbillivirus Paramyxovirus Pneumovirus Heniparvirus

Question 26

Paramyxovirus family virus proteins

Answer 26

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

Question 27

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

Answer 27

cytoplasm

Question 28

Human Parainfluenza Viruses (HPIV) - key issues

Answer 28

* 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

Question 29

Paramyxoviridae - Respiratory Synctial virus (RSV)

Answer 29

* 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

Question 30

Disease mechanisms of Respiratory Syncytial Virus

Answer 30

* 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

Question 31

RSV - pathogenesis

Answer 31

Typical giant cells - pink intracytoplasmic inclusions

Question 32

Immune response in infants vs adults to RSV

Answer 32

* 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

Question 33

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

Answer 33

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

Question 34

Human Metapneumovirus - hMPV (Characteristics)

Answer 34

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

Question 35

hMPV treatment and prevention

Answer 35

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

Question 36

Paramyxoviridae - Hendra and Nipah Virus

Answer 36

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

Question 37

Adenovirus (Characteristics)

Answer 37

* \>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

Question 38

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

Answer 38

military recruits