IRF-3 in the Cellular Response to Viral Infection

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Viral infections are a major threat to human life. Persistent and latent viruses have evolved mechanisms that allow them to effectively evade the normal host mechanisms for limiting or eliminating viral infections. These host cell mechanisms involve both the innate and adaptive immune systems. Members of both the herpesviruses and the papillomaviruses can establish long term latent and/or persistent infections in their natural hosts. Although adaptive immunity contributes significantly to the elimination of infection, the initial rapid innate immune response to a virus occurs at the level of infected cells to prevent the spread of the virus to neighboring cells. The transcriptional induction of interferon (IFN) -alpha and beta is central to the cellular antiviral response and occurs rapidly after infection. These cytokines have pleiotropic effects on both the infected and the uninfected neighboring cells, including inhibition of cell growth and the induction of cell death. In addition, type I interferons trigger a strong inflammatory response from the immune system at the site of infection. Such potency of the interferons is critical for the effective elimination of infection, but, if left uncontrolled, can result in extensive tissue damage. In recent years, complex regulatory mechanisms have been uncovered that govern the production of these cytokines. One of the proteins involved in sensing a viral infection and triggering the production of IFNs is Interferon Regulatory Factor-3 (IRF-3). In addition to its role in activating expression of the beta-interferon gene, IRF-3 has also been implicated in the induction of viral induced apoptosis. It is possible that IRF-3 as a regulator of the type 1 interferons may be a modulator of CTL immunity. We will explore this pathway and examine the mechanisms by which some viruses inactivate this pathway for the replication of the virus and the survival of the infected cell.