An immunosuppressed Syrian golden hamster model for SARS-CoV infection

Virology. 2008 Oct 25;380(2):312-21. doi: 10.1016/j.virol.2008.07.026. Epub 2008 Aug 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cricetinae
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacology
  • Disease Models, Animal*
  • Gene Deletion
  • Immunocompromised Host*
  • Immunosuppression / methods
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacology
  • Kidney / pathology
  • Lung / pathology
  • Mesocricetus
  • Myocardium / pathology
  • Nasal Cavity / pathology
  • SARS Virus / physiology*
  • Severe Acute Respiratory Syndrome*
  • Survival Analysis
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / physiology
  • Viral Proteins / genetics
  • Viral Proteins / physiology
  • Weight Loss

Substances

  • Immunosuppressive Agents
  • ORF7b protein, SARS coronavirus
  • Viral Matrix Proteins
  • Viral Proteins
  • sars7a protein, SARS virus
  • Cyclophosphamide