Respiratory Viruses Flashcards Preview

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Flashcards in Respiratory Viruses Deck (38):
1

Respiratory Viruses

Influenza virus

Rhinovirus

Coronavirus

Parainfluenza virus

Respiratory synctial virus

Metapneumovirus

Adenovirus (sometimes)

2

Virus families

  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)

 

3

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

4

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

5

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

6

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

7

Acute influenza infection in adults - symptoms

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

8

Acute influenza infection in children

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

9

Complications of influenza virus infection

Primary viral pneumonia

Secondary bacterial pneumonia

Myositis and cardiac involvement

Neurologic syndromes

10

Influenza diagnosis

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

11

Replication and Spread of influenza (7 steps)

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

12

What is the influenza virus cellular receptor?

Sialic acid

13

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

Lowers the pH which triggers fusion and release of contents

14

Prevention and control of influenza: Immunization

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

15

Prevention and control of influenza: Chemotherapy

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

16

Influenza is usually treated with a _______ vaccine

Trivalent

17

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

18

Rhinovirus symptoms

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

All due to inflammatory response

19

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

20

Rhinoviruses are transmitted via _______

fomites

21

Coronaviruses (characteristics)

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

Disesae limited to upper respiratory tract, infects epithelial cells

No vaccine available

22

Coronavirus Outbreaks

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

23

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

24

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

25

Paramyxoviridae Family

Morbillivirus

Paramyxovirus

Pneumovirus

Heniparvirus

26

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

A image thumb
27

Paramyxoviruses replicate in the ______

cytoplasm

28

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

29

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

30

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

31

RSV - pathogenesis

Typical giant cells - pink intracytoplasmic inclusions

32

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

33

RSV treatment prevention and control

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

34

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

35

hMPV treatment and prevention

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

36

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

 

37

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

38

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

military recruits