TRIM2, a novel host factor that restricts New World Arenavirus infection

新世界啮齿动物传播的出血热沙粒病毒（NWA），如Jun n病毒， 30%的死亡率 虽然有效的Junn病毒疫苗减少了疾病 发病率，散发病例以及其他已知和新的NWA， 没有疫苗或有效的治疗方法。由于它们是通过气溶胶传播的， 这些A类沙粒病毒也是潜在的生物恐怖剂。我们最近进行了一次 用携带Jun n糖蛋白的假型病毒进行siRNA筛选以找到宿主基因 参与了进入过程，可以作为治疗靶点我们发现了一些基因， 此前与病毒感染有关，包括TRIM 2，三重基序（TRIM）的成员 包括宿主对病毒感染的内在防御的众所周知的成员的家族。 我们发现TRIM2是一种抗病毒进入宿主因子。 除了它们的抗病毒活性之外， TRIM蛋白参与广泛的生物学功能，包括细胞增殖， 泛素化、细胞凋亡和各种人类病理学。在这里，我们将调查可能的 TRIM2通过实现以下目的限制NWA感染的新机制： 目的1：确定TRIM2影响Jun？n病毒感染的哪些步骤。 目的2：确定TRIM2如何限制Jun n病毒感染。 目的3：确定TRIM2是否限制体内Jun病毒感染。 这些研究将使我们能够定义TRIM2限制的潜在独特机制。 NWA感染，并将使我们能够开发关键试剂，用于未来在体内研究TRIM 2， 病毒感染和正常发育。

New world rodent-borne hemorrhagic fever arenaviruses (NWA) such as Jun¿n virus have about a 30% mortality rate. Although an effective Jun¿n virus vaccine has decreased disease incidence, sporadic cases of this as well as the other known and novel NWAs for which there are no vaccines or effective therapeutics still occur. Because they are transmitted by aerosols, these Category A arenaviruses are also potential bioterrorism agents. We recently performed a siRNA screen with pseudotyped viruses bearing the Jun¿n glycoprotein to find host genes involved in entry that could serve as therapeutic targets. We identified a number of genes not previously implicated in virus infection, including TRIM2, a member of the tripartite motif (TRIM) family that includes well-known members of the host's intrinsic defense against viral infections. We showed that TRIM2 is an anti-viral entry host factor. In addition to their antiviral activity, TRIM proteins are involved in a wide range of biological functions including cell proliferation, ubiquitinylation, apoptosis and a variety of human pathologies. Here we will investigate the likely novel mechanism by which TRIM2 restricts NWA infection by carrying out the following aims: Aim 1: Characterize which steps of Jun¿n virus infection are affected by TRIM2. Aim 2: Determine how TRIM2 restricts Jun¿n virus infection. Aim 3: Determine if TRIM2 restricts Jun¿n virus infection in vivo. These studies will allow us to define the potentially unique mechanism by which TRIM2 restricts NWA infection and will allow us to develop critical reagents for future in vivo studies of TRIM2 in virus infection and in normal development.