INHIBITION OF IRF7-MEDIATED INTERFERON SIGNAL TRANSDUCTION BY KSHV VIRF3

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在病毒感染后，宿主免疫系统的主要防御措施是激活干扰素(干扰素)介导的抗病毒途径，该途径由干扰素调节因子(IRFs)介导。为了完成自己的生命周期，病毒必须调节宿主干扰素介导的免疫反应。卡波西肉瘤相关疱疹病毒(KSHV)是一种人类致癌疱疹病毒，它通过掺入细胞内IRFs的病毒同源物，称为vIRFs，开发了一种独特的机制来对抗细胞内干扰素介导的抗病毒活性。在这里，我们报道了KSHV vIRF3的一种新的免疫逃避机制，以阻断细胞内IRF7介导的天然免疫来应对病毒感染。KSHV vIRF3与IRF7的DNA结合域或中心IRF结合结构域发生特异性相互作用，这种相互作用导致抑制IRF7的DNA结合活性，从而抑制IFNα的产生和干扰素介导的免疫。与艾滋病有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.