MATRIX PROTEIN AND RETROVIRUS INFECTION

描述：更好地了解逆转录病毒的重要性 复制周期，以确定病毒控制的新靶点， 势在必行 禽逆转录病毒劳斯肉瘤病毒（RSV），第一个病毒 与癌症有关，仍然是肿瘤逆转录病毒的原型。 这项建议 重点是RSV的主要结构蛋白之一，Gag 基质（MA）蛋白，在病毒感染。 关于导致病毒整合的事件知之甚少，这是病毒整合的关键步骤。 复制的 申请人实验室的工作表明，RSV MA 蛋白质可能在整合中起关键的、未描述的作用。 几种突变体 在MA内，发现了导致非感染性 粒子 在一类突变体中，有一个感染的晚期阻滞， 最有可能发生在融合之前。 第一特定 目的是检查MA是否参与整合。 第二类 突变体导致感染性阻断早得多的感染，之前 逆转录的起始。 第二个具体目标是 MA在受体结合和融合过程中也起作用的假设。 第三个具体目标将表征新的MA突变体， 使用来自MA结构和保守基序的信息创建。 的 第四个目标是研究病毒在感染过程中是如何与细胞相互作用的。 感染，并寻求确定病毒和细胞合作伙伴的MA期间 感染的早期阶段 所有这些研究都集中在 在逆转录病毒生命的一个重要部分， 周期

DESCRIPTION: The importance of better understanding the retroviral replication cycle in order to identify novel targets for viral control is imperative. The avian retrovirus Rous sarcoma virus (RSV), the first virus linked to cancer, remains the prototype oncoretrovirus. This proposal focuses on the role of one of the major RSV structural protein, the Gag matrix (MA) protein, in viral infection. Little is known about the events leading to viral integration, a key step in replication. Work from the applicant s laboratory suggests that the RSV MA protein may play a key, undescribed, role in integration. Several mutants within MA were identified that led to efficient production of noninfectious particles. In one class of mutants, there was a late bock to infection, most likely occurring immediately before integration. The first specific aim is to examine whether MA is involved in integration. A second class of mutants resulted in an infectivity block much earlier in infection, prior to the initiation of reverse transcription. The second specific aim addresses the hypothesis that MA also functions during receptor binding and fusion. The third specific aim will characterize new MA mutants which will be created using information from the MA structure and conserved motifs. The fourth aim will examine how the virus interfaces with the cell during infection and seeks to identify viral and cellular partners of MA during early stages of infection. All of these studies are centered on the activity of a single protein during an important part of the retroviral life cycle.