MATRIX PROTEIN AND RETROVIRUS INFECTION

描述：更好地了解逆转录病毒的重要性 为了识别病毒控制的新靶点，复制周期是 势在必行。禽类逆转录病毒劳斯肉瘤病毒(RSV)，第一种病毒 与癌症有关，仍然是肿瘤逆转录病毒的原型。这项建议 重点介绍RSV的主要结构蛋白之一Gag的作用 基质(MA)蛋白，在病毒感染中。 人们对导致病毒整合的事件知之甚少，这是 复制。申请人S实验室的工作表明，呼吸道合胞病毒MA 蛋白质可能在整合中扮演一个关键的、未被描述的角色。几个突变体 在MA中发现了导致高效生产非传染性的 粒子。在一类突变体中，感染发生的时间较晚， 最有可能发生在整合之前。第一个具体 目的是检查并购是否参与了整合。第二类 突变者在感染前更早地导致传染性阻断， 逆转录的启动。第二个具体目标是 MA在受体结合和融合过程中也发挥作用的假说。 第三个具体目标将描述新的MA突变体，这将是 利用MA结构和保守基序的信息创建。这个 第四个目标将检查病毒如何与细胞在 感染，并寻求确定MA的病毒和细胞伙伴 感染早期阶段。所有这些研究都集中在 逆转录病毒生命的重要部分中单个蛋白质的活性 周而复始。

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.