Mount Sinai School of Medicine
Emerging Viruses: Interferon-Antagonists and Virulence
Viruses have evolved ways to counteract the host innate immune response. Of particular importance are viral products which inhibit the antiviral activity of the type I interferon system. Such “interferon-antagonists” are essential for the virulence of several “model” viruses including influenza virus, Sendai virus, vaccinia virus and herpes simplex virus. We have developed new methods to screen viral proteins for the ability to counteract the interferon-induced antiviral response. One viral interferon-antagonist identified using such methods is the Ebola virus VP35 protein. We are currently elucidating the mechanism(s) by which VP35 exerts its anti-interferon effect. We are also screening proteins from other highly pathogenic human viruses for interferon-antagonist activity. Of particular interest is Lassa virus, an arenavirus endemic to West Africa that causes Lassa fever, a disease with high mortality and serious sequelae including hearing loss in survivors. Annually, there are an estimated 100-300 thousand cases of Lassa virus infection resulting in approximately 5,000 deaths. The identification of interferon-antagonists in such emerging pathogens will provide new insights into the mechanisms of viral pathogenesis and may ultimately provide insights into new antiviral strategies.