The cytoplasmic tail of the influenza A virus M2 protein plays a role in viral assembly
The cytoplasmic tail of the influenza A virus M2 protein plays a role in viral assembly
复制标题
DOI：
10.1128/jvi.00049-06
复制
发表时间：
2006-06-01
影响因子：
5.4
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
--
作者：
Iwatsuki-Horimoto, Kiyoko;Horimoto, Taisuke;Kawaoka, Yoshihiro
病毒复制周期以病毒组分组装形成子代病毒体结束。对于甲型流感病毒，基质M1蛋白和两种膜整合糖蛋白，血凝素和神经氨酸酶，在这一过程中协同发挥作用。在这里，我们问另一种膜蛋白，M2蛋白，是否在病毒组装中发挥作用。M2蛋白由97个氨基酸组成，在甲型流感病毒的三种跨膜蛋白中具有最长的胞质尾区（54个残基）。因此，我们通过反向遗传学产生了一系列M2胞质尾缺失突变体。我们发现从M2尾的羧基末端缺失超过22个氨基酸的突变体是可行的，但生长效率低于野生型病毒。对病毒体的分析表明，M2尾缺失超过22个羧基末端残基的病毒显然比野生型病毒含有更少的病毒核糖核蛋白复合物。这些M2尾部突变体在形态上也不同于野生型病毒：野生型病毒是球形的，而一些突变体是丝状的。丙氨酸扫描实验进一步表明，M2尾74 - 79位的氨基酸在病毒体形态发生中起作用，并影响病毒的感染性。我们的结论是，M2的甲型流感病毒的胞质结构域在病毒组装和形态发生中起着重要的作用。
The viral replication cycle concludes with the assembly of viral components to form progeny virions. For influenza A viruses, the matrix M1 protein and two membrane integral glycoproteins, hemagglutinin and neuraminidase, function cooperatively in this process. Here, we asked whether another membrane protein, the M2 protein, plays a role in virus assembly. The M2 protein, comprising 97 amino acids, possesses the longest cytoplasmic tail (54 residues) of the three transmembrane proteins of influenza A viruses. We therefore generated a series of deletion mutants of the M2 cytoplasmic tail by reverse genetics. We found that mutants in which more than 22 amino acids were deleted from the carboxyl terminus of the M2 tail were viable but grew less efficiently than did the wild-type virus. An analysis of the virions suggested that viruses with M2 tail deletions of more than 22 carboxy-terminal residues apparently contained less viral ribonucleoprotein complex than did the wild-type virus. These M2 tail mutants also differ from the wild-type virus in their morphology: while the wild-type virus is spherical, some of the mutants were filamentous. Alanine-scanning experiments further indicated that amino acids at positions 74 to 79 of the M2 tail play a role in virion morphogenesis and affect viral infectivity. We conclude that the M2 cytoplasmic domain of influenza A viruses plays an important role in viral assembly and morphogenesis.