IRF-3 in the Cellular Response to Viral Infection

病毒感染是人类生命的主要威胁。持续和潜伏的病毒已经进化出一种机制，使它们能够有效地避开限制或消除病毒感染的正常宿主机制。这些宿主细胞机制既涉及先天性免疫系统，也涉及获得性免疫系统。疱疹病毒和乳头状瘤病毒的成员都可以在其自然宿主中建立长期潜伏和/或持续感染。虽然获得性免疫对消除感染有重要作用，但最初对病毒的快速先天免疫反应发生在受感染的细胞水平上，以防止病毒的传播。 传给邻近的细胞。干扰素α和β的转录诱导是细胞抗病毒反应的中心，并在感染后迅速发生。这些细胞因子对感染和未感染的邻近细胞都有多效性作用，包括抑制细胞生长和诱导细胞死亡。此外，I型干扰素会在感染部位引发免疫系统的强烈炎症反应。干扰素的这种效力对于有效消除感染至关重要，但如果不加以控制，可能会导致广泛的组织损伤。近年来，人们发现了控制这些细胞因子产生的复杂调控机制。干扰素调节因子-3(IRF-3)是参与感知病毒感染和触发IFN产生的蛋白质之一。除了激活β-干扰素基因的表达外，IRF-3还参与了病毒诱导的细胞凋亡。IRF-3作为1型干扰素的调节因子，可能是CTL免疫的调节剂。我们将探索这一途径，并研究一些病毒使这一途径失活的机制，以促进病毒的复制和感染细胞的生存。

Viral infections are a major threat to human life. Persistent and latent viruses have evolved mechanisms that allow them to effectively evade the normal host mechanisms for limiting or eliminating viral infections. These host cell mechanisms involve both the innate and adaptive immune systems. Members of both the herpesviruses and the papillomaviruses can establish long term latent and/or persistent infections in their natural hosts. Although adaptive immunity contributes significantly to the elimination of infection, the initial rapid innate immune response to a virus occurs at the level of infected cells to prevent the spread of the virus to neighboring cells. The transcriptional induction of interferon (IFN) -alpha and beta is central to the cellular antiviral response and occurs rapidly after infection. These cytokines have pleiotropic effects on both the infected and the uninfected neighboring cells, including inhibition of cell growth and the induction of cell death. In addition, type I interferons trigger a strong inflammatory response from the immune system at the site of infection. Such potency of the interferons is critical for the effective elimination of infection, but, if left uncontrolled, can result in extensive tissue damage. In recent years, complex regulatory mechanisms have been uncovered that govern the production of these cytokines. One of the proteins involved in sensing a viral infection and triggering the production of IFNs is Interferon Regulatory Factor-3 (IRF-3). In addition to its role in activating expression of the beta-interferon gene, IRF-3 has also been implicated in the induction of viral induced apoptosis. It is possible that IRF-3 as a regulator of the type 1 interferons may be a modulator of CTL immunity. We will explore this pathway and examine the mechanisms by which some viruses inactivate this pathway for the replication of the virus and the survival of the infected cell.