SARS-CoV

The virus

  

Fig. 1 Sources: (Left) Department of Microbiology, The University of Hong Kong and the Government Virus Unit, Department of Health, Hong Kong SAR Chin (Right, click on the image to see larger figure) from wikipedia.org

 

  • Severe Acute Respiratory Syndrome (SARS) Coronavirus
  • emerged in China Nov. 2002
  • 8,437 infected cases (9 months, Nov. 2002 - Jul. 2003) 
  • 813 deaths
  • 29 countries
  • identified in April 2003
  • positive-sense RNA virus 
  • 30-32 kb ssRNA genome
  • largest of all RNA viruses
  • in Coronaviridae family
    • broad host range,
      • Animal coronaviruses:
        • Gastrointestinal, respiratory and systemic diseases. (avian infectious bronchitis, feline multi-organ infections (fatal), swine/bovine/turkey/canine enteritis)
      • Human coronaviruses:
        • Respiratory disease and gastroenteritis (lesser)
        • HCoV-OC43 and HCoV-229E cause common cold
        • HCoV-HKU1 and HCoV-NL63 (both are newer) cause more severe infections of the upper and lower respiratory tract (rarely fatal)
  • Enzootic virus in Southeast Asia
    • Animals appear to be infected by SARS-CoV
      • Masked palm civets (Paguma larvata)
      • Raccoon dogs (Melogale moschata) .
    • Specific reservoir not yet identified.
  • Symptoms:
    • influenza-like syndrome of malaise, rigors, fatigue, and high fevers
    • progress to atypical pneumonia (2 of 3 cases)
    • watery diarrhoea (in many) with virus shedding
  • The most common cause of death : respiratory failure
  • Severe cases:
    • lymphopaenia, neutrophilia, mild thrombocytopenia and coagulation defects (haemophagocytosis found in some)
  • Virus entry: Angiotensin-converting enzyme 2 (ACE2) receptor in lung & GI tract
  • Downregulates ACE2 expression by internalization after binding of SARS-CoV to ACE2. (ACE2 has a protective role during acute lung injury.) [see Fig. 2]
  • Role of ACE2 in reducing lung tissue damage in acute injury.
    • Angiotensin I (AT I) produced in an acute lung injury is converted to angiotensin II (AT II, potent chemical) by angiotensin-converting enzyme (ACE).  AT II binds to either receptor 1a (AT1aR) causing tissue damage and lung edema, or to receptor2 (AT2R) reducing tissue damage. Angiotensin-converting enzyme 2 (ACE2) in turn converts the potent AT II to a less damaging angiotensin1−7 (AT1−7). (rACE2 & ATA are external intervention, which are beyond the scope and, therefore, not explained here.)

 

Fig.2

Figure Source: John Nicholls & Malik Peiris Good ACE, bad ACE do battle in lung injury, SARS. Nature Medicine  11, 821 - 822 (2005)

 

  • SARS-CoV-infected T cells contribute to lymphopenia and to atrophy of spleen and lymphoid tissue.
  • Inhibit expression of type I interferon in infected monocyte-derived dendritic cells and macrophages due to IRF3, interferon-regulatory factor 3, is not activated (phosphorylated & dimerized).
  • Stimulate expression of chemokines: CXCL10, CCL2, CCL3, CCL5, & CCL8 (IL8=neutrophil attractant)  leading to influx of monocytes and/or macrophages.
  • Increase serum conc. of anti-inflammatory molecules (TGF-beta, PGE2).
  • Induce activation of p38MAPK in monocytes leading to increase of IL-6 (pro-inflammatory molecule).

 

Transmission

Fig. Source: World Health Organization Regional Office for the Western Pacific

 

 

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p38MAPK = p38 mitogen-activated protein kinase