SARS-CoV has been identified as the causative agent of an emerging human infectious disease, SARS. Its immunopathological mechanisms have not been fully characterized. One hypothesis is that the pathogenesis of SARS-CoV is caused by a disproportionate immune response, illustrated by elevated levels of inflammatory cytokines and chemokines, such as IP-10, MCP-1, IL-6 and IL-8. SARS-CoV has been shown in vitro to induce changes of cytokines and chemokines in various human and animal cells. We previously reported that interferon (IFN)-alfacon 1 was more active against SARS-CoV infection in Calu-3 cells than in African green monkey epithelial cells on day 3 post-infection. In the current study, we evaluated its efficacy of IFN-alfacon 1 in Calu-3 cells during the first 7 days of virus infection compared to its efficacy in Vero 76 cells, in which a more productive virus infection occurs. Calu-3 cells appeared to be more responsive to the antiviral effects induced by exogenous IFN than did Vero 76 cells. Furthermore, IP-10, an IFN-inducible white cell chemoattractant, was detected in Calu-3 cells after SARS-CoV infection. Interestingly, IP-10 expression was shown to be significantly elevated when SARS-CoV-infected Calu-3 cells were treated with IFN-alfacon 1. To our knowledge, this is the first time that the IP-10 expression has been clearly demonstrated in Calu-3 cells after SARS-CoV infection. Since IP-10 seems to be coordinated with a protective response in cells, we evaluated the efficacy of antivirals directed against SARS-CoV infection in BALB/c mice. IP-10 expression was detected in the lungs of SARS-CoV-infected BALB/c mice. Significantly high levels of mouse IP-10 in BALB/c mice was also detected when SARS-CoV-infected mice were treated with the interferon inducer, poly IC:LC. Our data might provide an important insight into the mechanism of pathogenesis of SARS-CoV and these properties might be therapeutically advantageous.
Acknowledgments: This work was supported by contracts NO1-A1-30048 and NO1-AI-15435 from the Virology Branch, NIAID, NIH.