Wednesday, February 19, 2014

mBio: Spread, Circulation, and Evolution of MERS-CoV


Distribution of MERS-CoV clades in time and space. - mBio


# 8313


Although MERS has receded from the headlines over the past couple of months, it continues to circulate in the Middle East, and occasionally jump to humans.   Exactly how it circulates, and how it jumps to humans, isn’t known – although recent research has pointed a finger at both camels and bats as being possible reservoir hosts for the virus.


Today, the open access journal mBio carries a review of what is known about the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), with an emphasis on the evolutionary changes observed in the virus over time. 


As the number of genetic sequences on deposit has increased, so have the number of MERS variants. None, however, have shown the kind of persistence one would associate with efficient human-to-human transmission.


The primary assumption is that the virus is maintained in an (as yet, unidentified) animal reservoir, and that intermittent spillovers from animal hosts to humans has resulted in localized clusters. But thus far, none of these outbreaks has demonstrated a basic reproductive number (R0) high enough (>1.0) to sustain an outbreak (see The Lancet: Transmissibility Of MERS-CoV for additional background).


R0 (pronounced R-nought) or Basic Reproductive Number.

Essentially, the number of new cases in a susceptible population likely to arise from a single infection. With an R0 below 1.0, a virus (as an outbreak) begins to sputter and dies out. Above 1.0, and an outbreak can have `legs’.


The authors do offer an alternative explanation, however, writing:


An alternative hypothesis is that the virus has now infected a sufficient number of humans to account for the observed distribution and diversity of the virus but the infection is asymptomatic in many individuals. A recent serosurvey of 363 individuals in the Saudi Arabia failed, however, to find MERS-CoV-seropositive individuals (13).


First a link to the study, and  some excerpts, after which I’ll have a bit more.


Spread, Circulation, and Evolution of the Middle East Respiratory Syndrome Coronavirus

Matthew Cottena, Simon J. Watsona, Alimuddin I. Zumlab,c,d, Hatem Q. Makhdoome, Anne L. Palsera, Swee Hoe Onga, Abdullah A. Al Rabeeahb, Rafat F. Alhakeemb, Abdullah Assirib, Jaffar A. Al-Tawfiqf, Ali Albarrakg, Mazin Barryh, Atef Shiblh, Fahad A. Alrabiahi, Sami Hajjari, Hanan H. Balkhyj, Hesham Flembank, Andrew Rambautl,m, Paul Kellama,c,d, Ziad A. Memishb,n


The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections.

Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012).

Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection.

Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1



MERS-CoV adaptation toward higher rates of sustained human-to-human transmission appears not to have occurred yet. While MERS-CoV transmission currently appears weak, careful monitoring of changes in MERS-CoV genomes and of the MERS epidemic should be maintained. The observation of phylogenetically related MERS-CoV in geographically diverse locations must be taken into account in efforts to identify the animal source and transmission of the virus.



In conclusion, the rapid identification and isolation of cases, combined with an R0 of less than 1, may control the human-to-human transmission as long as the virus transmission properties remain the same. Full control of the MERS epidemic requires identification of the source of infections to prevent the initiation of the observed human-to-human transmission chains.

(Continue . . . )


The conclusion is simply an academic’s way of saying, so far, we’ve been lucky with this virus.

It didn’t come fully transmissible `out of the box’, and it still requires some evolutionary tweaking before it can spark a greater epidemic threat. 


But each human infection is another opportunity for MERS-CoV to `figure us out’, and the big challenge right now is to find the reservoir host of the virus (camels, bats, baboons, rodents, etc. . . ) in order to stop these spillovers before the virus learns to adapt to us.


I’ll leave it to Dr. Vincent Racaniello or Dr. Ian Mackay to parse and interpret the more technical aspects of this study, as a lot of it is truly above my pay grade. 


In the meantime, for some additional background on MERS, check out some of Ian’s recent  blogs on the topic:


Middle East respiratory syndrome coronavirus (MERS-CoV): summing up 100 weeks
Monkey magic: Vero cells make more MERS-CoV RNA than any other animal's...
MERS-CoV antibodies in dromedary camels from Dubai, UAE, as far back as 2005...
A date with Middle East respiratory syndrome coronavirus (MERS-CoV)..

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