An immunosuppressed Syrian golden hamster model for SARS-CoV infection

Virology
Volume 380, Issue 2, 25 October 2008, Pages 312-321

Scott R. Schaecher, Jennifer Stabenow, Christina Oberle, Jill Schriewer, R. Mark Buller, John E. Sagartz, Andrew Pekosz.

Abstract

Several small animal models have been developed for the study of severe acute respiratory syndrome coronavirus (SARS-CoV) replication and pathogenesis. Syrian golden hamsters are among the best small animal models, though little clinical illness and no mortality are observed after virus infection. Cyclophosphamide was used to immunosuppress hamsters leading to a prolonged disease course and higher mortality after SARS-CoV infection. In addition, there was a significant weight loss, expanded tissue tropism, and increased viral pathology in the lung, heart, kidney, and nasal turbinate tissues. Infection with recombinant SARS-CoV viruses bearing disruptions in the gene 7 coding region showed no significant change in replication kinetics, tissue tropism, morbidity, or mortality suggesting that the ORF7a (7a) and ORF7b (7b) proteins are not required for virus replication in immunosuppressed hamsters. This modified hamster model may provide a useful tool for SARS-CoV pathogenesis studies, evaluation of antiviral therapy, and analysis of additional SARS-CoV mutants.

Keywords

SARS-CoV, Coronavirus, Cyclophosphamide, ORF7a, ORF7b, Hamster, Accessory gene, Pathogenesis