Bart L. Haagmans and Albert D. M. E. Osterhaus are in the Department of Virology, Erasmus Medical Center, Rotterdam, Netherlands.
The authors have declared that no competing interests exist.
Osterhaus and Haagmans discuss a new study in
Severe acute respiratory syndrome (SARS) first emerged in Guangdong Province, the People's Republic of China, in November 2002. The disease was characterised by a rapidly progressive atypical pneumonia [
In typical cases, which were largely confined to adult and elderly individuals, SARS presented with acute respiratory distress syndrome (ARDS)—characterised by the presence of diffuse alveolar damage (DAD) upon autopsy. The pathological changes in lung alveoli most likely follow a common pathway characterised by an acute phase of protein-rich alveolar fluid influx into the alveolar lumina as a consequence of the injury to the alveolar wall. Subsequently, type-2 pneumocyte (see
SARS-CoV was detected not only in the respiratory tract but also in faeces and urine of patients. Replication of the virus in the gastrointestinal tract was confirmed by electron microscopic studies of biopsies of the upper and lower intestinal mucosae of patients with SARS. Faecal transmission proved to be important in at least one major community outbreak in Hong Kong, in which over 300 patients were infected within a few days [
Development of animal models for SARS-CoV infection of humans is of utmost importance to elucidate the pathogenesis of SARS and to develop intervention strategies against the infection. A wide range of animal species is susceptible to experimental infection with SARS-CoV, including rodents (mice and hamsters), carnivores (ferrets and cats), and nonhuman primates (cynomolgus and rhesus macaques, common marmosets, and African green monkeys) [
In contrast, SARS-CoV inoculation in the respiratory tract of cynomolgus macaques causes infection of bronchial epithelial cells, type-1 and type-2 pneumocytes at one to four days postinfection, followed by extensive type-2 pneumocyte hyperplasia in the lungs at four to six days postinfection [
Syncytia (indicated by the arrowhead) in the lumen of a bronchiole (A) and expression of SARS-CoV antigen by a syncytium in the lumen of an alveolar duct (B).
(Figure derived from Figures 1 and 3 in [
Studies from different laboratories confirmed that nonhuman primates could be infected experimentally with SARS-CoV, although the severity of the induced lung pathology varied and clinical signs were generally not reported. So far, factors underlying these differences have not been delineated, but virus strain, age, microbiological state, genetic background, and origin of the animals could have played a role.
In this issue of
The persistent threat of a possible new introduction of SARS-CoV or of a related virus in the human population necessitates further refinement of animal models to elucidate the pathogenesis of, and intervention strategies against, SARS. Although none of the current animal models have fully reproduced all features of SARS, the most important aspects of SARS are observed in experimentally infected nonhuman primates. Such models have already demonstrated the protective effect of pre- and postexposure use of pegylated human interferon-α, of candidate SARS-CoV vaccines, and of convalescent sera from SARS patients (unpublished results; [
acute respiratory distress syndrome
diffuse alveolar damage
severe acute respiratory syndrome
SARS coronavirus