Characterization of DAI during MCMV infection




Landsteiner, Vanessa J.

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Pathogen recognition initiates host cell defense mechanisms including activation of the innate immune system in an effort to clear an infection. As a survival mechanism, viruses have developed potent strategies to evade the host response. Viruses that persist for the life of their host, such as herpesviruses, are particularly adept at modulating host innate immunity to benefit the virus. Previous work has shown that receptor interacting protein kinase (RIP)3-dependent programmed necrosis is a critical host response toward murine cytomegalovirus (MCMV) infection, and this pathway is actively inhibited during infection by the MCMV M45 gene product, also known as vIRA. IRA inhibits the association of RIP3 with the DNA-dependent activator of interferon regulatory factors (DAI/ZBP-1), clearly implicating DAI in this pathway. In addition to programmed necrosis, DAI has also been implicated in the antiviral immune response toward herpesviruses. However, the mechanisms by which DAI mediates these functions during viral infection remain largely unexplored. Using the MCMV model, we have further characterized the role of DAI in the host innate immune response to MCMV infections.


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