Influenza A Virus Can Undergo Multiple Cycles of Replication without M2 Ion Channel Activity
Influenza A Virus Can Undergo Multiple Cycles of Replication without M2 Ion Channel Activity
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DOI：
10.1128/jvi.75.12.5656-5662.2001
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发表时间：
2001-06
影响因子：
5.4
通讯作者：
Tokiko Watanabe;Shinji Watanabe;Hiroshi Ito;H. Kida;Y. Kawaoka
中科院分区：
文献类型：
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作者：
Tokiko Watanabe;Shinji Watanabe;Hiroshi Ito;H. Kida;Y. Kawaoka
离子通道蛋白是细胞的常见成分，甚至在一些病毒中也被发现。例如，甲型流感病毒的M2蛋白具有质子离子通道活性，被认为在病毒复制中发挥重要作用。由于缺乏对该功能的直接支持，我们试图产生具有缺陷M2离子通道活性的病毒。出乎意料的是，在体外实验中，M2离子通道活性明显丧失的突变体在细胞培养中复制的效率与野生型病毒一样高。我们还生成了一个含有M2蛋白的嵌合突变体，其跨膜结构域被血凝素糖蛋白取代。这种病毒在细胞培养中复制得相当好，但在小鼠中没有生长。最后，缺乏M2蛋白跨膜和细胞质结构域的突变体在细胞培养中生长不良，在小鼠中没有生长。因此，甲型流感病毒可以在没有负责离子通道活性的M2跨膜结构域的情况下经历多个复制周期，尽管这种活性促进了病毒的有效复制。
ABSTRACT Ion channel proteins are common constituents of cells and have even been identified in some viruses. For example, the M2 protein of influenza A virus has proton ion channel activity that is thought to play an important role in viral replication. Because direct support for this function is lacking, we attempted to generate viruses with defective M2 ion channel activity. Unexpectedly, mutants with apparent loss of M2 ion channel activity by an in vitro assay replicated as efficiently as the wild-type virus in cell culture. We also generated a chimeric mutant containing an M2 protein whose transmembrane domain was replaced with that from the hemagglutinin glycoprotein. This virus replicated reasonably well in cell culture but showed no growth in mice. Finally, a mutant lacking both the transmembrane and cytoplasmic domains of M2 protein grew poorly in cell culture and showed no growth in mice. Thus, influenza A virus can undergo multiple cycles of replication without the M2 transmembrane domain responsible for ion channel activity, although this activity promotes efficient viral replication.