FUNCTIONS OF THE INFLUENZA C VIRUS CM2 AND P31 PROTEINS

C 型流感病毒 CM2 和 P31 蛋白的功能

• 批准号: 6012922
• 负责人: Andrew S. Pekosz
• 金额: $ 3.13万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6012922
• 关键词: Golgi apparatus; Orthomyxoviridae; cell component structure /function; electrophysiology; host organism interaction; intracellular transport; membrane channels; protein degradation; protein localization; protein structure function; protein transport; site directed mutagenesis; virus protein; virus replication; voltage /patch clamp

Influenza A and B viruses are responsible for high levels of morbidity and mortality in the human population every year. Influenza C virus infection causes a mild upper respiratory disease in humans, with a seroprevalence of over 90 percent in the adult human population. This research proposal aims to study and characterize the influenza C virus life cycle by investigating the CM2 and the newly identified p31 viral proteins. The CM2 protein is believed to be the influenza C virus homolog of the influenza A virus M2 protein, a known ion channel that aids in the dissassembly of influenza A virus during entry into susceptible cells. I will characterize the effect of CM2 on the intracellular transport of integral membrane glycoproteins, as well as the Golgi morphology of CM2 expressing cells. Site-directed mutagenesis will be used in an attempt to disrupt the biological activity of CM2 without perturbing the oligomerization and surface transport of the protein. Whole cell patch-clamping of CM2 expressing eukaryotic cells will be performed in order to identify and characterize any potential ion channel activity of CM2. Finally, the pathway and signals involved in influenza C virus p31 protein degradation will be investigated. These studies should significantly further our understanding of the influenza C virus life cycle, and provide new insights into virus-host cell interactions.

甲型和B型流感病毒是每年人类群体中高水平发病率和死亡率的原因。丙型流感病毒感染会导致人类轻度上呼吸道疾病，在成年人群中血清阳性率超过90%。 该研究计划旨在通过研究CM 2和新发现的p31病毒蛋白来研究和表征丙型流感病毒的生命周期。 CM 2蛋白被认为是甲型流感病毒M2蛋白的丙型流感病毒同源物，M2蛋白是一种已知的离子通道，有助于甲型流感病毒在进入易感细胞期间解体。我将描述CM 2对整合膜糖蛋白的细胞内转运的影响，以及CM 2表达细胞的高尔基体形态。将使用定点诱变来尝试破坏CM 2的生物活性，而不干扰蛋白质的寡聚化和表面转运。 将对表达CM 2的真核细胞进行全细胞膜片钳，以鉴定和表征CM 2的任何潜在离子通道活性。 最后，将研究参与丙型流感病毒p31蛋白降解的途径和信号。 这些研究将大大加深我们对丙型流感病毒生命周期的理解，并为病毒-宿主细胞相互作用提供新的见解。