Growth of influenza A virus is not impeded by simultaneous removal of the cholesterol-binding and acylation sites in the M2 protein.
Growth of influenza A virus is not impeded by simultaneous removal of the cholesterol-binding and acylation sites in the M2 protein.
复制标题
同时去除 M2 蛋白中的胆固醇结合位点和酰化位点不会阻碍甲型流感病毒的生长
DOI：
10.1099/vir.0.038554-0
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Herrmann
中科院分区：
文献类型：
--
作者：
Tielesch;Möller;Schmitt;Bannert;Herrmann
流感病毒的装配和出芽发生在“budozone”中，budozone是质膜中的一个合并的筏结构域。病毒跨膜蛋白M2与病毒颗粒断裂有关，这是病毒出芽的最终步骤，可能是通过将两亲性螺旋楔形插入膜中。为了做到这一点，假设M2通过酰化和胆固醇结合介导靶向Budozone的边缘。最近显示，酰化和胆固醇结合影响M2的胞质尾区的膜缔合和蛋白质靶向聚结筏。本研究检测了M2两亲性螺旋中酰化位点（C50）和胆固醇识别/相互作用氨基酸共有基序（关键残基Y 52和Y 57）的联合去除是否会影响病毒形成。重组流感病毒是在流感病毒株A/WSN/33背景下产生的，这些特征中的一个或两个都有突变。与野生型相比，所有突变病毒在各种细胞类型中显示出非常相似的生长动力学。野生型和突变型病毒在其相对M2含量上不同，但在主要结构蛋白方面没有差异。病毒的形态不受突变M2的影响。此外，野生型和突变型病毒在感染细胞中表现出相当的竞争适应性。最后，M2序列的全球比较显示，存在具有缺乏两个脂质缔合基序的M2的天然病毒株。总之，这些结果表明，M2中的酰化和胆固醇结合基序对于流感病毒在细胞培养物中的复制并不重要，这表明其他因素可以将M2靶向至出芽位点。
Influenza virus assembly and budding occur in the ‘budozone’, a coalesced raft domain in the plasma membrane. The viral transmembrane protein M2 is implicated in virus particle scission, the ultimate step in virus budding, probably by wedge-like insertion of an amphiphilic helix into the membrane. In order to do this, M2 is hypothesized to be targeted to the edge of the budozone, mediated by acylation and cholesterol binding. It was recently shown that acylation and cholesterol binding affect the membrane association of the cytoplasmic tail of M2 and targeting of the protein to coalesced rafts. This study tested whether combined removal of the acylation site (C50) and the cholesterol recognition/interaction amino acid consensus motifs (key residues Y52 and Y57) in the amphiphilic helix of M2 influenced virus formation. Recombinant influenza viruses were generated in the influenza strain A/WSN/33 background with mutations in one or both of these features. In comparison with the wild-type, all mutant viruses showed very similar growth kinetics in various cell types. Wild-type and mutant viruses differed in their relative M2 content but not regarding the major structural proteins. The morphology of the viruses was not affected by mutating M2. Moreover, wild-type and mutant viruses showed comparable competitive fitness in infected cells. Lastly, a global comparison of M2 sequences revealed that there are natural virus strains with M2 devoid of both lipid-association motifs. Taken together, these results indicate that the acylation and cholesterol-binding motifs in M2 are not crucial for the replication of influenza virus in cell culture, indicating that other factors can target M2 to the budding site.
登录
查看更多内容
影响因子：
2.9
作者：
Nguyen, Phuong A.;Soto, Cinque S.;Polishchuk, Alexei;Caputo, Gregory A.;Tatko, Chad D.;Ma, Chunlong;Ohigashi, Yuki;Pinto, Lawrence H.;DeGrado, William F.;Howard, Kathleen P.
通讯作者：
Howard, Kathleen P.
影响因子：
3.7
作者：
Rossman JS;Lamb RA
通讯作者：
Lamb RA
DOI：
10.1083/jcb.200412058
发表时间：
2005-06-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hess ST;Kumar M;Verma A;Farrington J;Kenworthy A;Zimmerberg J
通讯作者：
Zimmerberg J
甲型流感病毒的M2蛋白被酰化。
DOI：
10.1099/0022-1317-72-6-1461
发表时间：
1991
期刊：
The Journal of general virology
影响因子：
--
作者：
M. Veit;H. Klenk;A. Kendal;R. Rott
通讯作者：
R. Rott
流感病毒M2蛋白胞质尾部的内在膜关联和胆固醇结合和棕榈酰化调节的侧膜分选
DOI：
10.1042/bj20110706
发表时间：
2011
期刊：
The Biochemical journal
影响因子：
--
作者：
Leventhal;Herrmann;Veit M.
通讯作者：
Veit M.