The New Age of Virus Discovery: Genomic Analysis of a Novel Human Betacoronavirus Isolated from a Fatal Case of Pneumonia

Holmes, Kathryn V.; Dominguez, Samuel R.

D uring the past decade, at least 9 novel human respiratory viral pathogens have been discovered, primarily by using highly sensitive nucleotide sequencing and new virus detection technologies. These human viruses include human metapneumovirus, rhinoviruses in clade C, bocavirus, polyomaviruses WU and KI 2009 pandemic H1N1 influenza virus, and 3 new human coronaviruses (HCoV). Until 2003, only two coronaviruses, HCoV-OC43 and HCoV-229E, were known to cause human disease, primarily upper respiratory tract infections. The discovery of severe acute respiratory syndrome-CoV (SARS-CoV) as the cause of the SARS pandemic of 2002 to 2003 demonstrated the epidemic potential of this large family of RNA viruses and emphasized their importance in human respiratory diseases. After the SARS pandemic, two additional human coronaviruses, NL63 and HKU1, were identified and found to cause both upper and lower respiratory tract disease. Although these coronaviruses were only recently discovered, they have probably been circulating in the human population worldwide for a long time. HCoV-OC43 apparently jumped from a bovine host into humans more than 100 years ago and has become endemic worldwide. In contrast, the SARS pandemic was caused by a novel human virus that had very recently emerged into the human population from its zoonotic reservoirs, Chinese horseshoe bats (suborder Microchiroptera, family Rhinolophidae, genus Rhinolophus) (1, 2) . Indeed, extensive phylogenetic studies suggest that all alpha-and beta coronaviruses may be derived from bat coronaviruses (3).