Regulated MAVS-mediated signaling in KSHV lytic replication

University Of Southern California, Los Angeles CA

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Abstract

Abstract Innate immune response is the first line of defense against invading pathogens. The cytosolic RIG-I receptor is defined as a pattern recognition receptor for viral RNA. Upon binding to RNA, RIG-I dimerizes with its downstream mitochondrion antiviral signaling (MAVS) adaptor protein to initiate innate immune signaling that culminates in antiviral cytokine production, thus establishing an antiviral state. Human herpesviruses are one of the most ubiquitous pathogens that cause pronounced diseases in immunocompromised individuals. Kaposi's sarcoma-associated herpesvirus (KSHV) is the leading causative agent in morbidity and mortality in AIDS patients. Recently, we have found that KSHV infection also activates the RIG-I- and MAVS-dependent innate immune pathway. However, KSHV hijacks these signaling cascades to promote viral infection. This exploratory project aims to address the molecule mechanism by which KSHV manipulates the MAVS adaptor molecule to prevent antiviral interferon production. Our work will define an intricate immune evasion strategy deployed by a stealthy lymphotropic virus and reveal key viral and host factors that may be targeted for antiviral therapy.