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.

Keywords: Alphacoronavirus; Betacoronavirus; Chiroptera; Coronaviridae; Livestock; Respiratory tract infections; Rodentia; Zoonotic diseases.

Fig. 1

Summary diagram of the animal groups representing natural hosts and the putative intermediate hosts for the six CoVs found in humans.

Fig. 2

Genome characteristics and mutation patterns of HCoV-229E and related viruses from animals. (A) Maximum-likelihood phylogeny of complete genomes of representative HCoV-229E-related coronaviruses from humans, camelids, and bats. Filled circles at nodes indicate bootstrap supports of 100% (200 replicates). HCoV-NL63 GenBank (accession no. NC_005831) was used as an outgroup (branch truncated). (B) Genomic organization of 229E-related coronaviruses. Regions with deletions are given in red. (C and D) Deletion patterns in ORF 8 homologs of 229E-related coronaviruses regions with deletions are given in red (numbered I–IV). Asterisks represent triplets that would act as in-frame stop codons; arrows represent possible start codons.

Fig. 3

Maximum-likelihood phylogeny of complete genomes of representatives of Betacoronavirus 1, Mouse Hepatitis virus (MHV), and HCoV-HKU1 strains from humans and animals. Virus designations include GenBank accession numbers and host information. ICTV species are given to the right of clade designations. Filled circles at nodes indicate bootstrap supports of 100% (200 replicates). SARS-CoV (accession no. NC_004718) was used as an outgroup (branch truncated). PHEV; porcine hemagglutinating encephalomyelitis virus.