Virology
Volume 395, Issue 2, 20 December 2009, Pages 210-222
Craig W. Day, Ralph Baric, Sui Xiong Cai, Matt Frieman, Yohichi Kumaki John D. Morrey, Donald F. Smee, Dale L. Barnard.
Abstract
Severe acute respiratory syndrome (SARS) is a highly lethal emerging disease caused by coronavirus SARS-CoV. New lethal animal models for SARS were needed to facilitate antiviral research. We adapted and characterized a new strain of SARS-CoV (strain v2163) that was highly lethal in 5- to 6-week-old BALB/c mice. It had nine mutations affecting 10 amino acid residues. Strain v2163 increased IL-1α, IL-6, MIP-1α, MCP-1, and RANTES in mice, and high IL-6 expression correlated with mortality. The infection largely mimicked human disease, but lung pathology lacked hyaline membrane formation. In vitro efficacy against v2163 was shown with known inhibitors of SARS-CoV replication. In v2163-infected mice, Ampligen™ was fully protective, stinging nettle lectin (UDA) was partially protective, ribavirin was disputable and possibly exacerbated disease, and EP128533 was inactive. Ribavirin, UDA, and Ampligen™ decreased IL-6 expression. Strain v2163 provided a valuable model for anti-SARS research.
Keywords
SARS-CoV, Lethal, IL-6, Ribavirin, Ampligen™, UDA, Protease inhibitor, Cytokine, Chemokine, Mouse