This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated anti-viral pathway that is mediated by interferon regulatory factors (IRFs). In order to complete their life cycle, viruses must modulate host IFN-mediated immune response. Kaposi's sarcoma-associated herpesvirus (KSHV), a human tumor-inducing herpesvirus, has developed a unique mechanism for antagonizing cellular IFN-mediated anti-viral activity by incorporating viral homologs of the cellular IRFs, called vIRFs. Here, we report a novel immune evasion mechanism of KSHV vIRF3 to block cellular IRF7-mediated innate immunity in response to viral infection. KSHV vIRF3 specifically interacts with either the DNA binding domain or the central IRF association domain of IRF7 and this interaction leads to the inhibition of IRF7 DNA binding activity, thereof suppression of IFNalpha production and IFN-mediated immunity. AIDS related.
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