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Hosts and Sources of Endemic Human Coronaviruses.

ABSTRACT: The four endemic human coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 contribute a considerable share of upper and lower respiratory tract infections in adults and children. While their clinical representation resembles that of many other agents of the common cold, their evolutionary histories, and host associations could provide important insights into the natural history of past human pandemics. For two of these viruses, we have strong evidence suggesting an origin in major livestock species while primordial associations for all four viruses may have existed with bats and rodents. HCoV-NL63 and -229E may originate from bat reservoirs as assumed for many other coronaviruses, but HCoV-OC43 and -HKU1 seem more likely to have speciated from rodent-associated viruses. HCoV-OC43 is thought to have emerged from ancestors in domestic animals such as cattle or swine. The bovine coronavirus has been suggested to be a possible ancestor, from which HCoV-OC43 may have emerged in the context of a pandemic recorded historically at the end of the 19th century. New data suggest that HCoV-229E may actually be transferred from dromedary camels similar to Middle East respiratory syndrome (MERS) coronavirus. This scenario provides important ecological parallels to the present prepandemic pattern of host associations of the MERS coronavirus.

SUBMITTER: Corman VM

PROVIDER: S-EPMC7112090 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Hosts and Sources of Endemic Human Coronaviruses.

Corman Victor M VM Muth Doreen D Niemeyer Daniela D Drosten Christian C

Advances in virus research 20180216

The four endemic human coronaviruses HCoV-229E, -NL63, -OC43, and -HKU1 contribute a considerable share of upper and lower respiratory tract infections in adults and children. While their clinical representation resembles that of many other agents of the common cold, their evolutionary histories, and host associations could provide important insights into the natural history of past human pandemics. For two of these viruses, we have strong evidence suggesting an origin in major livestock species ...[more]

PMID: 29551135

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Project description:Community protective immunity can affect RNA virus evolution by selecting for new antigenic variants on the scale of years, exemplified by the need of annual evaluation of influenza vaccines. The extent to which this process termed antigenic drift affects coronaviruses remains unknown. Alike the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seasonal human coronaviruses (HCoV) likely emerged from animal reservoirs as new human pathogens in the past. We therefore analyzed the long-term evolutionary dynamics of the ubiquitous HCoV-229E and HCoV-OC43 in comparison with human influenza A virus (IAV) subtype H3N2. We focus on viral glycoprotein genes that mediate viral entry into cells and are major targets of host neutralizing antibody responses. Maximum likelihood and Bayesian phylogenies of publicly available gene datasets representing about three decades of HCoV and IAV evolution showed that all viruses had similar ladder-like tree shapes compatible with antigenic drift, supported by different tree shape statistics. Evolutionary rates inferred in a Bayesian framework were 6.5 × 10-4 (95% highest posterior density (HPD), 5.4-7.5 × 10-4) substitutions per site per year (s/s/y) for HCoV-229E spike (S) genes and 5.7 × 10-4 (95% HPD, 5-6.5 × 10-4) s/s/y for HCoV-OC43 S genes, which were about fourfold lower than the 2.5 × 10-3 (95% HPD, 2.3-2.7 × 10-3) s/s/y rate for IAV hemagglutinin (HA) genes. Coronavirus S genes accumulated about threefold less (P < 0.001) non-synonymous mutations (dN) over time than IAV HA genes. In both IAV and HCoV, the average rate of dN within the receptor binding domains (RBD) was about fivefold higher (P < 0.0001) than in other glycoprotein gene regions. Similarly, most sites showing evidence for positive selection occurred within the RBD (HCoV-229E, 6/14 sites, P < 0.05; HCoV-OC43, 23/38 sites, P < 0.01; IAV, 13/15 sites, P = 0.08). In sum, the evolutionary dynamics of HCoV and IAV showed several similarities, yet amino acid changes potentially representing antigenic drift occurred on a lower scale in endemic HCoV compared to IAV. It seems likely that pandemic SARS-CoV-2 evolution will bear similarities with IAV evolution including accumulation of adaptive changes in the RBD, requiring vaccines to be updated regularly, whereas higher SARS-CoV-2 evolutionary stability resembling endemic HCoV can be expected in the post-pandemic stage.

Project description:Four coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E) are endemic in human populations. All these viruses are seasonal and generate short-term immunity. Like the highly pathogenic coronaviruses, the endemic coronaviruses have zoonotic origins. Thus, understanding the evolutionary dynamics of these human viruses might provide insight into the future trajectories of SARS-CoV-2 evolution. Because the zoonotic sources of HCoV-OC43 and HCoV-229E are known, we applied a population genetics-phylogenetic approach to investigate which selective events accompanied the divergence of these viruses from the animal ones. Results indicated that positive selection drove the evolution of some accessory proteins, as well as of the membrane proteins. However, the spike proteins of both viruses and the hemagglutinin-esterase (HE) of HCoV-OC43 represented the major selection targets. Specifically, for both viruses, most positively selected sites map to the receptor-binding domains (RBDs) and are polymorphic. Molecular dating for the HCoV-229E spike protein indicated that RBD Classes I, II, III, and IV emerged 3-9 years apart. However, since the appearance of Class V (with much higher binding affinity), around 25 years ago, limited genetic diversity accumulated in the RBD. These different time intervals are not fully consistent with the hypothesis that HCoV-229E spike evolution was driven by antigenic drift. An alternative, not mutually exclusive possibility is that strains with higher affinity for the cellular receptor have out-competed strains with lower affinity. The evolution of the HCoV-OC43 spike protein was also suggested to undergo antigenic drift. However, we also found abundant signals of positive selection in HE. Whereas such signals might result from antigenic drift, as well, previous data showing co-evolution of the spike protein with HE suggest that optimization for human cell infection also drove the evolution of this virus. These data provide insight into the possible trajectories of SARS-CoV-2 evolution, especially in case the virus should become endemic.

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Hosts and Sources of Endemic Human Coronaviruses.

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Hosts and Sources of Endemic Human Coronaviruses.

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