Abstract
While dromedaries are the immediate animal source of Middle East Respiratory Syndrome (MERS) epidemic, viruses related to MERS coronavirus (MERS-CoV) have also been found in bats as well as hedgehogs. To elucidate the evolution of MERS-CoV-related viruses and their interspecies transmission pathway, samples were collected from different mammals in China. A novel coronavirus related to MERS-CoV, Erinaceus amurensis hedgehog coronavirus HKU31 (Ea-HedCoV HKU31), was identified from two Amur hedgehogs. Genome analysis supported that Ea-HedCoV HKU31 represents a novel species under Merbecovirus, being most closely related to Erinaceus CoV from European hedgehogs in Germany, with 79.6% genome sequence identity. Compared to other members of Merbecovirus, Ea-HedCoV HKU31 possessed unique non-structural proteins and putative cleavage sites at ORF1ab. Phylogenetic analysis showed that Ea-HedCoV HKU31 and BetaCoV Erinaceus/VMC/DEU/2012 were closely related to NeoCoV and BatCoV PREDICT from African bats in the spike region, suggesting that the latter bat viruses have arisen from recombination between CoVs from hedgehogs and bats. The predicted HKU31 receptor-binding domain (RBD) possessed only one out of 12 critical amino acid residues for binding to human dipeptidyl peptidase 4 (hDPP4), the MERS-CoV receptor. The structural modeling of the HKU31-RBD-hDPP4 binding interphase compared to that of MERS-CoV and Tylonycteris bat CoV HKU4 (Ty-BatCoV HKU4) suggested that HKU31-RBD is unlikely to bind to hDPP4. Our findings support that hedgehogs are an important reservoir of Merbecovirus, with evidence of recombination with viruses from bats. Further investigations in bats, hedgehogs and related animals are warranted to understand the evolution of MERS-CoV-related viruses.
Highlights
In 2012, the Middle East Respiratory Syndrome (MERS) first emerged and 27 countries have been affected with 2458 confirmed cases, together with a 34.5% fatality rate [1]
We discovered a novel species of Merbecovirus, Ea-HedCoV HKU31, in Amur hedgehogs from
This “hedgehog” branch was closely related to NeoCoV and BatCoV PREDICT from African bats in the spike region
Summary
In 2012, the Middle East Respiratory Syndrome (MERS) first emerged and 27 countries have been affected with 2458 confirmed cases, together with a 34.5% fatality rate [1]. In 2018, these four Betacoronavirus lineages were reclassified into five subgenera, namely Embecovirus, Sarbecovirus, Merbecovirus, Nobecovirus, and an additional subgenus, Hibecovirus [17]. Four of the six CoVs known to infect humans belong to Betacoronavirus, with human CoV HKU1 and OC43 belonging to Embecovirus, Severe Acute Respiratory Syndrome CoV (SARS-CoV) belonging to Sarbecovirus and MERS-CoV belonging to Merbecovirus [18,19,20,21,22,23,24,25]. The bloom in the discovery of novel animal CoVs since the SARS epidemic has uncovered bats as an important reservoir for alphacoronaviruses and betacoronaviruses, whereas birds are reservoirs responsible for gammacoronaviruses and deltacoronaviruses [14,26]
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