Because coronaviruses have relatively high mutation and RNA recombination rates and rapidly undergo cross species transmission events in vitro and in vivo (Baric et al., 1999 (Baric et al., , 1997 Treshman et al., 1996) , we and others in the field have speculated that coronaviruses might be important emerging pathogens as early as 1996 (Baric et al., 1996) . Notably, several major coronavirus pandemics had been recorded over the past 25 years in economically important animal species. In 1978, porcine epidemic coronavirus (PEDV) emerged and has remained among the most important causes of severe gastroenteritis in swine in Europe and Asia. Sequence analysis suggested that PEDV likely evolved from human coronaviruses (Bridgen et al., 1993; Duarte and Laude, 1994) . In 1984, the less pathogenic porcine respiratory coronaviruses (PRCV) evolved from the highly virulent enteric strain, transmissible gastroenteritis virus (TGEV) (Pensaert et al., 1986) . This was accomplished by either a single nucleotide mutation or deletion in the major surface glycoprotein gene, spike (Sanchez et al., 1999; Wesley et al., 1991) . Currently, PRCV affords some level of cross protection against TGEV (van Nieuwstadt et al., 1989; Wesley et al., 1991) , although more virulent forms of PRCV have recently emerged (Saif, 1999) . A closely related arterivirus, the porcine respiratory and reproductive disease virus (PRRSV), emerged in the late 1980s in Canada and Europe, and is currently the most important swine pathogen worldwide, responsible for economic losses of $200 million/year in the US alone (Blaha, 2000; Rossow, 1998) . In 1992, a new respiratory pathogen was recognized that caused 'shipping fever' in cattle, a severe, oftentimes fatal, pneumonia. Sequence analysis suggests that "shipping fever" was caused by a respiratory bovine coronavirus (BCV-R), which likely evolved from an enteric bovine coronavirus by acquiring mutations in S and the replicase gene (Storz et al., 2000) . Concordant with this hypothesis, sequence comparisons have now indicated that host shifts, even between distant avian and mammalian species, are common events in coronavirus phylogeny (Rest and Mindell, 2003) .