Coronaviruses cause a substantial fraction of human colds and a host of common respiratory infections in many other animals, including economically important diseases of livestock, poultry, and laboratory rodents. Moreover, although these viruses were not known for producing more than mild infections in humans prior to the SARS epidemic, veterinary coronavirologists have long been aware of their potential for producing lethal infections in animals, as Linda Saif describes in this chapter’s first paper. For this reason, there is already an extensive amount of research on animal coronaviruses that can be drawn from for understanding the life cycle and pathogenicity of the SARS virus, and veterinary scientists are now being called on to join the research response to the epidemic and share their knowledge of coronaviruses with a broader audience. Mark Denison’s paper describes the current state of research on animal coronaviruses and discusses how results from these animal models suggest promising directions for future research on SARS and other emerging zoonoses.

Animal coronaviruses tend to follow one of two basic pathogenic models, producing either enteric or respiratory infections. Both models show parallels to the clinical features of SARS patients, the majority of whom presented with respiratory infections but in some cases also suffered from enteric complications. In adult animals, coronavirus infections of a respiratory nature have shown increased severity in the presence of several factors, including high exposure doses, respiratory coinfections, stress related to shipping or commingling with animals from different farms, and treatment with corticosteroids. In young, seronegative animals, enteric coronaviruses can cause fatal infections. Although coronaviruses generally cause disease in a single animal species, some have been demonstrated to cross species barriers.

Considerable effort has already been applied toward uncovering an animal source of the SARS virus. This has been sought primarily through the genetic characterization of viral isolates from suspected animal sources and comparison with human SARS coronavirus samples. In the past, however, epidemiological detective work has identified the source of many outbreaks of infectious disease, and one workshop participant suggested that a case control study of the first 50 to 100 SARS patients from China’s Guangdong Province, where the earliest cases of the disease were detected, might prove similarly fruitful. While a natural reservoir for the SARS virus has not yet been identified, the combination of such genomic and epidemiological techniques is already yielding suggestive results. For example, the last paper in this chapter by Yi Guan et al. describes the presence of coronaviruses closely related to SARS among live animals sold in Guangdong markets. Similar epidemiological principles may yet provide valuable direction for further laboratory surveys of animal viruses aimed at finding the original source and reservoir of the SARS coronavirus.

Coronaviruses have been classified into three major categories based on their genetic characteristics. While the SARS virus has been linked with Group II coronaviruses, whose members include human and bovine respiratory viruses and the mouse hepatitis virus, there is still some debate over whether its genetic features might be sufficiently distinct to warrant classification within a separate, fourth class of coronaviruses. Studies of coronavirus replication at the molecular level reveal several mechanisms that account for the repeated, persistent infections typical of coronaviral disease. High rates of mutation and RNA-RNA recombination produce viruses that are able to adapt to acquire and regain virulence. Although researchers have identified several potential targets for antiviral therapies, the ability of the virus to mutate and recombine represents a major challenge to vaccine development. A vaccine that can provide highly effective, long-term protection against respiratory coronavirus infections has not yet been developed, nor have appropriate animal models been developed to test potential vaccines against SARS. It was noted by several workshop participants that a coordinated, multidisciplinary research effort, drawing on expertise in both the veterinary and biomedical sciences, will likely be needed to meet these goals.