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“Smart, Smarter, and Smartest Herpesviruses: How to Evade Host Immune System” Moon Jung Song, Ph.D. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University ABSTRACT In immune and tissue cells, pattern-recognition receptors (PRRs) detect and respond to virus infection by rapidly inducing interferons (IFNs) to initiate antiviral responses, therefore serving as the first line of host innate immune defense. In parallel, viruses have developed clever strategies to actively subvert the PRRs and the IFNs signaling pathways for their own benefit. Herpesviruses establish life- long persistent infection and interact with hosts through the latency-and-reactivation cycle. Murine gammaherpesvirus-68 (MHV-68 or HV-68) has recently emerged as a small animal model system for the study of human gammaherpesvirus pathogenesis and host-virus interactions. We have established a random transposon-inserted mutant library of MHV-68 for identification of genes required for virus replication in vitro and in vivo. Using this mutant library and an expression library of all MHV-68 viral genes, we sought to identify viral genes that evade from the host IFN response. Our screening results indicate that MHV-68 encodes multiple immune evasion genes that may interplay in blocking IFNinduced ISRE activation as well as the production of the type I IFNs at different steps. In this seminar, our current understandings of viral immune evasion in PRR signaling pathways will be discussed using an example in MHV-68.