Friday, 20 September 2013

Molecular epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV)

And a newcomer to the MERS-CoV birthday celebrations! What great timing to have this released today.

The Lancet paper accompanying those recent partial and full genome sequences has been released form its cage. It's a collaborative effort by authors affiliated with the Global Centre for Mass Gatherings Medicine (Ministry of Health Saudi Arabia), Welcome Trust Sanger Institute (United Kingdom) and many other locations.

A few highlights of the largest MERS-CoV molecular epidemiology study to date, which includes some great transmission figures and trees (hat tip to the graphics people at Lancet):
  • Genetic diversity analyses 3 distinct genotypes were identified from human cases in Riyadh 
  • The Al-Ahsa hospital cluster may have had more than 1 viral introduction
  • Other clusters and standalnone cases can be representd as distinct genoytpes of MERS-CoV, posisbly indicating multiple different virus acquisitions from different sources
  • Predictive evolutionary analysis suggests an evolutionary rate of 6.3x10-4 substitutions per nucleotide site per year suggesting a time to the most recent common viral ancestor was July 2011 (ranging from July 2007- June 2012). So we can rule out my harebrained "What If.." MERS-CoV was an endemic virus that we had only just discovered
  • This evolutionary rate of change suggest more than 1 jump from animal to human was the cause of the outbreak. Unlikely to be just a single introduction followed by human-to-human transmission across Saudi Arabia and beyond. This also reduced any possible R0 value (the number of cases that 1 case generates, on average, over it's period of infectivity) since transmission events were not a continuous chain but likely to be multiple different spillovers
  • The rates also suggest it's been substantial period since these viruses shared a common ancestor - so an intermediate host is still a likely culprit for spillover into humans (ongoing studies are examining camels, bats, goats, sheep, dogs, cats, rodents and others - no baboons?)
  • Contact with goats and camels has been reported in some cases and we know that camels from Oman and Egypt have antibodies to a MERS-CoV-like virus
  • A particular change in the Spike protein that may impact on its role as a site for enzymatic cleavage (by endosomal furin or trypsin-like proteases) should be further examined (codon 1020; all recent MERS-CoV S protein differ here from the EMC/2012 strain of MERS-CoV exported to the Erasmus Medical Center researchers).
The authors conclude it is imperative that a better understanding of the exposures causing these spillover events be identified.