SARS: Evolution of a Virus

SARS: Evolution of a Virus

  • In November 2002 a mysterious pneumonia was seen in the Guangdong Province of China, but the first case of this new type of pneumonia was not reported until February 2003.
  • Thanks to the ease of global travel, it took only a couple of months for the pneumonia to spread to more than 25 countries in Asia, Europe, and North and South America.
  • This newly emergent pneumonia was labeled “severe acute respiratory syndrome” (SARS), and its causative agent was identified as a previously unrecognized coronavirus (CoV), the SARS-CoV.
  • Almost 10% of the roughly 8,000 people with SARS died.

  • However, once the epidemic was contained, the virus appeared to “die out,” and with the exception of a few mild, sporadic cases in 2004, no additional cases have been identified.
  • From where does a newly emergent virus come? And why did this viral disease apparently disappear?
  • Coronaviruses are large, enveloped viruses with positive strand RNA genomes. They are known to infect a variety of mammals and birds.
  • Researchers suspected that SARS-CoV had “jumped” from its animal host to humans.
  • To test this hypothesis, samples of animals at open markets in Guangdong were taken for nucleotide sequencing.
  • These studies revealed that cat like animals called masked palm civets (Paguma larvata) harbored variants of the SARS-CoV.
Cat like animals called masked palm civets
  • Although thousands of civets were then slaughtered, further studies failed to find widespread infection of domestic or wild civets.
  • In addition, experimental infection of civets with human SARS-CoV strains made these animals ill, making the civet an unlikely candidate for the reservoir species.
  • Such a species would be expected to harbor SARS-CoV without symptoms so that it could efficiently spread the virus.
  • Bats are reservoir hosts of several zoonotic viruses (viruses spread from animals to people).
  • Thus it was perhaps not too surprising when in 2005 two groups of international scientists independently demonstrated that Chinese horseshoe bats (genus Rhinolophus) are the natural reservoir of a SARS like coronavirus.
  • When the genomes of the human and bat SARS-CoV are aligned, 92% of the nucleotides are identical.
  • More revealing is alignment of the translated amino acid sequences of the proteins encoded by each virus.
  • The amino acid sequences are 96 to 100% identical for all proteins except the receptor-binding spike proteins, which are only 64% identical.
  • The SARS-CoV spike protein mediates both host cell surface attachment and membrane fusion.
  • Thus a mutation of the spike protein allowed the virus to “jump” from bat host cells to those of another species.
  • It is not clear if the SARS-CoV was transmitted directly to humans (bats are eaten as a delicacy, and bat feces are a
    traditional Asian cure for asthma) or if transmission to humans occurred through infected civets.
  • The region of the SARS-CoV spike protein that binds to the host receptor, angiotensin-converting enzyme-2 (ACE2), forms a shallow pocket into which ACE2 rests.
  • The region of the spike protein that makes this pocket is called the receptor binding domain (RBD).
  • Approximately 220 amino acids within the RBD, only four differ between civet and human.
  • Two of these amino acids appear to be critical.
(a) T human host cell receptor ACE2. (b) The civet SARS-CoV has two different amino acids at positions 479 and 487. This spike protein binds very poorly to human ACE2, thus the receptor is only weakly activated. (c) The spike protein on the human SARS-CoV that was isolated from patients in 2003 and 2004 also differs from that seen in the epidemic-causing SARS-CoV by two amino acids. This SARS-CoV variant caused only mild, sporadic cases.
  • Compared to the spike RBD in the SARS-CoV that caused the 2002-2003 epidemic, the civet spike has a serine (S) substituted for a threonine (T) at position 487 (T487S) and a lysine (K) at position 479, instead of asparagine (N), N479K.
  • This causes a thousand-fold decrease in the capacity of the virus to bind to human ACE2.
  • Furthermore, the spike found in SARS-CoV isolated from patients in 2003 and 2004 also has a serine at position 487 as well as a proline (P) for leucine (L) substitution at position 472 (L472P).
  • These amino acid substitutions could be responsible for the reduced virulence of the virus found in these more recent infections.
  • In other words, these mutations could be the reason the SARS virus appears to have “died out.”

Reference and Sources

  • https://www.researchgate.net/publication/7570445_Bats_Are_Natural_Reservoirs_of_SARS-Like_Coronaviruses
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875893/
  • https://covid.us.org/2020/06/29/yes-the-coronavirus-really-is-that-bad/
  • https://en.wikipedia.org/wiki/History_of_viruses

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