Subfamily: Orthocoronavirinae

Genus: Betacoronavirus

Distinguishing features

Betacoronaviruses form a distinct monophyletic group in the Orthocoronavirinae subfamily. Their nsp1 is distinct in size and sequence from the alphacoronavirus nsp1 and has no obvious counterpart in either deltacoronaviruses or gammacoronaviruses. Various sets of accessory genes are observed in different members (Figure 1.Betacoronavirus). Several betacoronaviruses infect humans with high transmissibility and/or fatality rate, including severe acute respiratory syndrome coronavirus (SARS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and Middle East respiratory syndrome-related coronavirus (Drosten et al., 2003, Ksiazek et al., 2003, van Boheemen et al., 2012, Zaki et al., 2012, Zhu et al., 2020). Similar to alphacoronaviruses, betacoronaviruses can infect a wide range of mammals.

Figure 1.Betacoronavirus Betacoronavirus genome organization. Comparison of the 3′-terminal genomic regions downstream of ORF1b of betacoronaviruses representative of different subgenera. ORFs are depicted as coloured boxes with green, HE; red, S; cyan, E; yellow, M and magenta, N. ORFs for accessory proteins are depicted as coloured boxes in grey.

Virion

Proteins

The unique hemagglutinin-esterase protein found in members of the subgenus Embecovirus can serve as a lectin and a receptor-destroying enzyme (de Groot 2006, Lang et al., 2020). This protein is capable of reversible attachment to O-acetylated sialic acid and hence can prevent the loss of infectivity due to off-target receptor binding (Zeng et al., 2008). Loss of hemagglutinin-esterase lectin function is observed in both human coronavirus OC43 and human coronavirus HKU1 (Bakkers et al., 2017).

Genome organization and replication

Members of subgenus Embecovirus contain a hemagglutinin-esterase (HE) gene, located between ORF1 and S genes. It is exclusively found in embecoviruses, suggesting possible heterologous recombination between the ancestor of embecoviruses and influenza C virus (family Orthomyxoviridae) (de Groot 2006, Zeng et al., 2008).

Bat Hp-betacoronavirus Zhejiang2013, found in the bat Hipposideros pratti, is the only member of the subgenus Hibecovirus (Wu et al., 2016a) and has an additional ORF2 located downstream of ORF1 and upstream of the S gene that is not found in other members of the genus Betacoronavirus. Detailed molecular characterization of this virus has yet to be done.

Biology

Similar to alphacoronaviruses, betacoronaviruses have diverse mammalian hosts. For the subgenus Embecovirus, members of the species Betacoronavirus 1 and China rattus coronavirus HKU24 have been identified from rat (Rattus norvegicus), Murine coronavirus from mice, Myodes coronavirus 2JL14 from rodents and Human coronavirus HKU1 from humans (Cheever et al., 1949, Woo et al., 2005, Lau et al., 2014, Wu et al., 2018). Cross-species jumping has been observed for members of the species Betacoronavirus 1 as these have been found in multiple mammalian hosts, including sable antelopes, bovines, waterbucks, dogs, white-tailed deer, dromedary camels, pigs and humans (Woo et al., 2014, Bakkers et al., 2017). Notably, no embecoviruses have been discovered in bats, suggesting that a rodent-related coronavirus may be the origin of this subgenus. Bats are the only host for members of the subgenera Hibecovirus and Nobecovirus. Merbecoviruses have been identified in bats, hedgehogs, camels and humans (Woo et al., 2007, Corman et al., 2014, Haagmans et al., 2014, Raj et al., 2014, Lau et al., 2018b, Lau et al., 2019), including Middle East respiratory syndrome coronavirus, the etiological agent of the on-going MERS epidemic (Zaki et al., 2012, de Groot et al., 2013). The subgenus Sarbecovirus includes two pathogenic viruses, SARS-CoV and SARS-CoV-2, responsible for the SARS epidemic in 2003 and the ongoing COVID-19 pandemic respectively (Drosten et al., 2003, Ksiazek et al., 2003, Zhu et al., 2020). SARS-CoV is able to infect humans, bats and palm civets (Lau et al., 2005, Li et al., 2005b). SARS-CoV-2 has a much wider host tropism than SARS-CoV (Nyberg et al., 2022) and has been found in bats, pangolins, cats, tigers, lions, snow leopards, cougars, pumas, ferrets, otters, gorillas, dogs, mice, hamsters, rabbits and mink. Most of these hosts are considered as inefficient or dead-end infections, except for the bi-directional transmission between mink/hamsters and humans (Wong et al., 2021, Yen et al., 2022).

Subgenus demarcation criteria

Details correspond to the family descriptions.

Species demarcation criteria

Details correspond to the family descriptions.