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MERS-CoV recombination: implications about the reservoir and potential for adaptation.

ABSTRACT: Recombination is a process that unlinks neighboring loci allowing for independent evolutionary trajectories within genomes of many organisms. If not properly accounted for, recombination can compromise many evolutionary analyses. In addition, when dealing with organisms that are not obligately sexually reproducing, recombination gives insight into the rate at which distinct genetic lineages come into contact. Since June 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 1,106 laboratory-confirmed infections, with 421 MERS-CoV-associated deaths as of 16 April 2015. Although bats are considered as the likely ultimate source of zoonotic betacoronaviruses, dromedary camels have been consistently implicated as the source of current human infections in the Middle East. In this article, we use phylogenetic methods and simulations to show that MERS-CoV genome has likely undergone numerous recombinations recently. Recombination in MERS-CoV implies frequent co-infection with distinct lineages of MERS-CoV, probably in camels given the current understanding of MERS-CoV epidemiology.

SUBMITTER: Dudas G

PROVIDER: S-EPMC4989901 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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MERS-CoV recombination: implications about the reservoir and potential for adaptation.

Dudas Gytis G Rambaut Andrew A

Virus evolution 20160120 1

Recombination is a process that unlinks neighboring loci allowing for independent evolutionary trajectories within genomes of many organisms. If not properly accounted for, recombination can compromise many evolutionary analyses. In addition, when dealing with organisms that are not obligately sexually reproducing, recombination gives insight into the rate at which distinct genetic lineages come into contact. Since June 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 1,1 ...[more]

PMID: 27774293

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Project description:BackgroundPlMERS-CoV is a coronavirus known to cause severe disease in humans, taxonomically classified under the subgenus Merbecovirus. Recent findings showed that the close relatives of MERS-CoV infecting vespertillionid bats (family Vespertillionidae), named NeoCoV and PDF-2180, use their hosts' ACE2 as their entry receptor, unlike the DPP4 receptor usage of MERS-CoV. Previous research suggests that this difference in receptor usage between these related viruses is a result of recombination. However, the precise location of the recombination breakpoints and the details of the recombination event leading to the change of receptor usage remain unclear.MethodsWe used maximum likelihood-based phylogenetics and genetic similarity comparisons to characterise the evolutionary history of all complete Merbecovirus genome sequences. Recombination events were detected by multiple computational methods implemented in the recombination detection program. To verify the influence of recombination, we inferred the phylogenetic relation of the merbecovirus genomes excluding recombinant segments and that of the viruses' receptor binding domains and examined the level of congruency between the phylogenies. Finally, the geographic distribution of the genomes was inspected to identify the possible location where the recombination event occurred.ResultsSimilarity plot analysis and the recombination-partitioned phylogenetic inference showed that MERS-CoV is highly similar to NeoCoV (and PDF-2180) across its whole genome except for the spike-encoding region. This is confirmed to be due to recombination by confidently detecting a recombination event between the proximal ancestor of MERS-CoV and a currently unsampled merbecovirus clade. Notably, the upstream recombination breakpoint was detected in the N-terminal domain and the downstream breakpoint at the S2 subunit of spike, indicating that the acquired recombined fragment includes the receptor-binding domain. A tanglegram comparison further confirmed that the receptor binding domain-encoding region of MERS-CoV was acquired via recombination. Geographic mapping analysis on sampling sites suggests the possibility that the recombination event occurred in Africa.ConclusionTogether, our results suggest that recombination can lead to receptor switching of merbecoviruses during circulation in bats. These results are useful for future epidemiological assessments and surveillance to understand the spillover risk of bat coronaviruses to the human population.

Dataset Information

MERS-CoV recombination: implications about the reservoir and potential for adaptation.

Publications

MERS-CoV recombination: implications about the reservoir and potential for adaptation.

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