Albert D. M. E. Osterhaus (
The authors have declared that no competing interests exist.
In response to our Perspective on nonhuman primate models for SARS [
As demonstrated by several groups, SARS coronavirus (SARS-CoV) replicates to high titers in the respiratory tract of a surprisingly broad range of animal species, albeit showing remarkable differences in cell tropism. We have argued that efficient infection of type 1 and 2 pneumocytes as seen in macaques and humans—most likely due to the similarities in the spike protein binding domains of the host SARS-CoV receptor ACE2—is a prerequisite for the SARS-CoV infection–induced pathology observed in humans. So far there is no strong evidence that a similar tropism is observed in other animal species.
However, the tropism of SARS-CoV for pneumocytes may not suffice to induce severe clinical signs in primates. In case of a resolving infection in macaques, pathological changes are evident four to six days after infection and may have become inapparent by days 12–14. In addition, in young adult humans, SARS-CoV infection generally causes relatively mild disease. Viral sequence differences in the SARS-CoV isolate HKU 39849 obtained from and distributed to several groups by Peiris et al. [
The apparent differences observed in clinical outcome of the infection in macaques, which is similar to the outcome in humans, may limit the utility of SARS-CoV–infected macaques as a model for severe SARS. However, none of the other models available produces clinical disease related to respiratory distress, except for ferrets that are inoculated with the HKU 39849 virus intratracheally [