e Recently, we reported the discovery of three novel coronaviruses, bulbul coronavirus HKU11, thrush coronavirus HKU12, and munia coronavirus HKU13, which were identified as representatives of a novel genus, Deltacoronavirus, in the subfamily Coronavirinae. In this territory-wide molecular epidemiology study involving 3,137 mammals and 3,298 birds, we discovered seven additional novel deltacoronaviruses in pigs and birds, which we named porcine coronavirus HKU15, white-eye coronavirus HKU16, sparrow coronavirus HKU17, magpie robin coronavirus HKU18, night heron coronavirus HKU19, wigeon coronavirus HKU20, and common moorhen coronavirus HKU21. Complete genome sequencing and comparative genome analysis showed that the avian and mammalian deltacoronaviruses have similar genome characteristics and structures. They all have relatively small genomes (25.421 to 26.674 kb), the smallest among all coronaviruses. They all have a single papain-like protease domain in the nsp3 gene; an accessory gene, NS6 open reading frame (ORF), located between the M and N genes; and a variable number of accessory genes (up to four) downstream of the N gene. Moreover, they all have the same putative transcription regulatory sequence of ACACCA. Molecular clock analysis showed that the most recent common ancestor of all coronaviruses was estimated at approximately 8100 BC, and those of Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus were at approximately 2400 BC, 3300 BC, 2800 BC, and 3000 BC, respectively. From our studies, it appears that bats and birds, the warm blooded flying vertebrates, are ideal hosts for the coronavirus gene source, bats for Alphacoronavirus and Betacoronavirus and birds for Gammacoronavirus and Deltacoronavirus, to fuel coronavirus evolution and dissemination.

Although human coronavirus OC43-OC43 (HCoV-OC43Coronaviruses cause infections in a wide variety of animals, resulting in respiratory, enteric, hepatic, and neurological diseases of various levels of severity. Based on genotypic and serological characterization, coronaviruses traditionally were classified into three distinct groups, groups 1, 2, and 3 (4). Recently, the Coronavirus Study Group of the International Committee for Taxonomy of Viruses has renamed the traditional group 1, 2, and 3 coronaviruses as Alphacoronavirus, Betacoronavirus, and Gammacoronavirus, respectively (http: //talk.ictvonline.org/media/p/1230.aspx).The recent severe acute respiratory syndrome (SARS) epidemic due to SARS coronavirus (SARS-CoV) and the identification of SARS-related coronaviruses (SARSr-CoVs) from Himalayan palm civets and horseshoe bats in mainland China have led to a boost in interest in the study of coronaviruses in both humans and animals (5,13,24,26,33,37,55). Before the SARS epidemic in 2003, there were only 19 known coronaviruses, including 2 human, 13 mammalian, and 4 avian coronaviruses. After the SARS epidemic, more than 20 additional novel coronaviruses have been described with complete genome sequences (9, 24-26, 31, 42, 45, 50, 53, 54, 57). These include 3 human coronaviruses, 15 mammalian coronaviruses, and 4 avian coronaviruses. For human coronaviruses, human coronavirus NL63 (HCoV-NL63) (an alphacoronavirus) and human coronavirus HKU1 (HCoV-HKU1) (a betacoronavirus) have been discovered in addition to the two previously known human coronaviruses, human coronavirus 229E (HCoV-229E) (an alphacoronavirus) and human coronavirus OC43 (HCoV-OC43) (a betacoronavirus), as well as SARSCoV (a betacoronavirus) (9,45,53,56). While HCoV-229E and HCoV-OC43 were thought to account for 5 to 30% of human respiratory tract infections, HCoV-NL63 and HCoV-HKU1 often were detected in Ͻ5% of respiratory tract samples (23,29,38). Outbreaks due to HCoV-OC43 also have been reported (3,32,44). Nevertheless, the different HCoVs often cocirculate, with one or two HCoVs being predominant depending on the geographical area and year (8,11,19,23).Coronaviruses are unique in having a high frequency of homologous RNA recombination, which is a result of random

While the novel Middle East respiratory syndrome coronavirus (MERS-CoV) is closely related to