In the mid-sixties of the previous century, the first two human coronaviruses (HCoV) were identified: HCoV-229E and HCoV-OC43 (29, 50, 70). These two human coronaviruses were studied extensively from approximately 1965 to the mid-1980s (7, 37, 49, 50, 57, 70). HCoV-229E is a member of the group I coronaviruses, and HCoV-OC43 is a member of group II. Besides the human coronaviruses, there are several group I and group II animal coronaviruses that infect cattle, pigs, cats, dogs, mice, and other animals (33). There is one additional branch, the group III coronaviruses, which are found exclusively in birds (33).

By infecting healthy volunteers, researchers learned that infection with HCoV-229E or HCoV-OC43 results in a common cold (7, 8, 29), and since then, HCoVs have been considered to be relatively harmless respiratory pathogens. This image was roughly disturbed when severe acute respiratory syndrome (SARS)-CoV was introduced into the human population in the winter of 2002 to 2003 in China. SARS-CoV causes a severe respiratory illness with high morbidity and mortality (16, 40). The virus originated from a wild-animal reservoir, most likely bats (43, 46), and was transmitted to humans via infected civet cats. The epidemic was halted in 2003 by a highly effective global public health response, and SARS-CoV is not currently circulating in humans. However, the SARS outbreak brought coronaviruses back into the limelight, and a renewed interest in this virus family resulted in the identification of two more human coronaviruses. We discovered HCoV-NL63, a novel member of group I, in a child with bronchiolitis in The Netherlands (74). HCoV-HKU1, a novel group II virus from an adult with chronic pulmonary disease in Hong Kong, was described in 2005 (81). An animal model is currently lacking for these previously unknown viruses. Nevertheless, since the discovery of HCoV-NL63 and HCoV-HKU1, much knowledge about these viruses has been gained. Several groups have studied their worldwide spread, association with human disease, replication characteristics, genome organization, and genetic diversity.