Influenza virus assembly and virulence

超出所提供的空间。甲型流感病毒的组装涉及几个病毒成分在病毒感染细胞内预定位置的特异性相互作用。参与这一过程的病毒蛋白是疫苗产生以及病毒适应新宿主的关键成分，但在组装过程中的确切作用尚未确定或确定。反向遗传学技术和RNA干扰等新技术的应用，使得对组装过程的精确解剖和对病毒组装发生重要的精确功能域的确定成为可能。为了充分了解参与甲型流感病毒组装的病毒因子，将对参与病毒组装的M1（基质）和M2蛋白结构域进行详细的分子研究。M1和M2中的氨基酸序列在将蛋白靶向到病毒出芽位点中起重要作用。本文将阐明抗M2抗体介导的抑制甲型流感病毒出芽的机制，并对M1蛋白与M2细胞质尾部的特异性相互作用进行表征。最后，将在感染重组病毒的细胞中分析M1的细胞内定位，重组病毒携带的HA和NA蛋白突变阻止了它们与糖脂筏或顶膜的联系。将产生具有一种或几种病毒蛋白特异性突变的重组病毒，并以其对抗m2抗体的敏感性、抗病毒药物的敏感性和毒力为特征。这些研究应进一步阐明产生新的高毒力甲型流感病毒的机制，并进一步确定控制抗体和药物敏感性的相互作用。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. The assembly of influenza A virus involves the specific interaction of several viral components at a predetermined location within the virus-infected cell. The viral proteins involved in this process are key components in the generation of vaccines as well as in the adaption of virus to new hosts but precise roles in the assembly process have yet to be ascribed or identified. The application of reverse genetics techniques and new technologies such as RNA interference allows for the precise dissection of the assembly process and the determination of precise functional domains important for virus assembly to take place. To fully understand the viral factors involved in influenza A virus assembly, a detailed molecular investigation of the domains of the M1 (matrix) and M2 proteins involved in virus assembly will be undertaken. The amino acid sequences in M1 and M2 that are important in targeting the proteins to sites of virus budding will be identified. The mechanism behind the anti-M2 antibody mediated inhibition of influenza A virus budding will be elucidated and specific interactions between the M1 protein and the M2 cytoplasmic tail will be characterized. Finally, the intracellular localization of M1 will be analyzed in cells infected with recombinant viruses bearing mutations in the HA and NA proteins that prevent their association with glycolipid rafts or the apical membrane. Recombinant viruses bearing specific mutations in one or several viral proteins will be generated and characterized for their sensitivity to anti-M2 antibodies, antiviral drug sensitivity and virulence. These studies should shed additional light on the mechanisms responsible for the generation of new, highly virulent influenza A viruses as well as further define the interactions that govern antibody and drug sensitivity. PERFORMANCE SITE ========================================Section End===========================================