FUNCTIONS OF THE INFLUENZA C VIRUS CM2 AND P31 PROTEINS

甲型和乙型流感病毒每年在人类人口中造成高发病率和高死亡率。C型流感病毒感染在人类引起一种轻微的上呼吸道疾病，在成年人口中血清阳性率超过90%。这项研究计划旨在通过研究CM2和新发现的p31病毒蛋白来研究和表征C型流感病毒的生命周期。CM2蛋白被认为是C型流感病毒与甲型流感病毒M2蛋白的同源物，M2蛋白是一种已知的离子通道，有助于甲型流感病毒进入敏感细胞时的分解。我将研究CM2对完整膜糖蛋白在细胞内转运的影响，以及表达CM2的细胞的高尔基形态。定点突变将被用来试图在不干扰蛋白质的寡聚和表面运输的情况下破坏CM2的生物活性。将对表达CM2的真核细胞进行全细胞膜片钳，以鉴定和表征CM2的任何潜在的离子通道活性。最后，我们将研究C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C型流感病毒生命周期的理解，并为病毒与宿主细胞之间的相互作用提供新的见解。

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.