A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo.
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-1alpha, IL-6, MIP-1alpha, 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.
Day
Craig W
CW
Institute for Antiviral Research, Utah State University, UMC 5600, Logan, UT 84322-5600, USA.
Baric
Ralph
R
Cai
Sui Xiong
SX
Frieman
Matt
M
Kumaki
Yohichi
Y
Morrey
John D
JD
Smee
Donald F
DF
Barnard
Dale L
DL
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D016679:Genome, Viral; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D045473:Severe acute respiratory syndrome-related coronavirus / Q000502:physiology*; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D016207:Cytokines; D014764:Viral Proteins