Evidence for an Ancestral Association of Human Coronavirus 229E with Bats

Abstract

We previously showed that close relatives of human coronavirus 229E (HCoV-229E) exist in African bats. The small sample and limited genomic characterizations have prevented further analyses so far. Here, we tested 2,087 fecal specimens from 11 bat species sampled in Ghana for HCoV-229E-related viruses by reverse transcription-PCR (RT-PCR). Only hipposiderid bats tested positive. To compare the genetic diversity of bat viruses and HCoV-229E, we tested historical isolates and diagnostic specimens sampled globally over 10 years. Bat viruses were 5-and 6-fold more diversified than HCoV-229E in the RNA-dependent RNA polymerase (RdRp) and spike genes. In phylogenetic analyses, HCoV-229E strains were monophyletic and not intermixed with animal viruses. Bat viruses formed three large clades in close and more distant sister relationships. A recently described 229E-related alpaca virus occupied an intermediate phylogenetic position between bat and human viruses. According to taxonomic criteria, human, alpaca, and bat viruses form a single CoV species showing evidence for multiple recombination events. HCoV-229E and the alpaca virus showed a major deletion in the spike S1 region compared to all bat viruses. Analyses of four full genomes from 229E-related bat CoVs revealed an eighth open reading frame (ORF8) located at the genomic 3= end. ORF8 also existed in the 229E-related alpaca virus. Reanalysis of HCoV-229E sequences showed a conserved transcription regulatory sequence preceding remnants of this ORF, suggesting its loss after acquisition of a 229E-related CoV by humans. These data suggested an evolutionary origin of 229E-related CoVs in hipposiderid bats, hypothetically with camelids as intermediate hosts preceding the establishment of HCoV-229E. IMPORTANCEThe ancestral origins of major human coronaviruses (HCoVs) likely involve bat hosts. Here, we provide conclusive genetic evidence for an evolutionary origin of the common cold virus HCoV-229E in hipposiderid bats by analyzing a large sample of African bats and characterizing several bat viruses on a full-genome level. Our evolutionary analyses show that animal and human viruses are genetically closely related, can exchange genetic material, and form a single viral species. We show that the putative host switches leading to the formation of HCoV-229E were accompanied by major genomic changes, including deletions in the viral spike glycoprotein gene and loss of an open reading frame. We reanalyze a previously described genetically related alpaca virus and discuss the role of camelids as potential intermediate hosts between bat and human viruses. The evolutionary history of HCoV-229E likely shares important characteristics with that of the recently emerged highly pathogenic Middle East respiratory syndrome (MERS) coronavirus.

Discovery of a novel canine respiratory coronavirus support genetic recombination among betacoronavirus1

“…Recombination is a common phenomenon in coronaviruses and thought to contribute to the emergence of new pathotypes (Gorbalenya, 2008;Wang et al, 2015). Thus far, most of the recombination events of coronaviruses have been reported between species of the same group (Herrewegh et al, 1998;Keck et al, 1988), such as among the batassociated CoVs (Corman et al, 2014) and 229E-related CoVs (Corman et al, 2015), and the major recombination breakpoint has mainly been within the S gene. Genetic recombinant among alphacoronavirus 1 species frequently occurred, such as ferret coronaviruses (Lamers et al, 2016;Minami et al, 2016).…”

Cellular entry of the porcine epidemic diarrhea virus

“…1b) have a large deletion in the N-domain; iii) clinical isolates of HCoV-229E encode a relatively short spike protein of 1173 residues in length due to the apparent lack of the N-domain (Farsani et al, 2012). Recently, bat coronaviruses related to HCoV-229E have been isolated from hipposiderid bats, some of them encoding unusual large spike glycoproteins of 1571-1582 residues in length (Corman et al, 2015). Intriguingly, PSI-BLAST analysis indicates that these 229E-related bat coronaviruses carry two consecutive N-domain homologs in the first 425 residues part of their S protein − which we designated N1 and N2 − with 32% and 35% amino acid sequence identity to the N-domain of the HCoV-NL63 S protein, respectively (Fig.…”

Quantitative structure‐activity relationship and molecular docking revealed a potency of anti‐hepatitis C virus drugs against human corona viruses

“…While SARS fatality rate was 8%, MERS fatality rate was 36% (by 9th of November 2016, the number of laboratory confirmed infections was 1813 and the number of reported deaths was 645) . Six coronavirus strains were reported to be zoonotic (ie, transmission of infections from animals to humans is possible) . These human coronaviruses were 229E and NL63 (belonging to Alphacoronavirus ) and OC43, HKU1, SARS, and MERS (belonging to Betacoronavirus ) .…”