Identification of Novel Influenza A Virus Proteins Translated from PA mRNA
Identification of Novel Influenza A Virus Proteins Translated from PA mRNA
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DOI：
10.1128/jvi.02656-12
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发表时间：
2013-03-01
影响因子：
5.4
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
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作者：
Muramoto, Yukiko;Noda, Takeshi;Kawaoka, Yoshihiro
甲型流感病毒的生命周期中涉及许多复制事件，它们是由具有特定功能的不同病毒蛋白完成的。然而，由于流感病毒基因组的大小有限，该病毒使用不同的机制来表达来自单个基因片段的多个病毒蛋白。M2和NS2蛋白是通过剪接产生的，最近发现了几种新的甲型流感病毒蛋白，如PB1-F2，PB1-N40和PA-X。在这里，我们在甲型流感病毒感染的细胞中发现了新的PA相关蛋白。这些新发现的蛋白质是从PA mRNA的第11和第13位密码子翻译而来的，因此是PA的N端截短形式，我们分别将其命名为PA-N155和PA-N182。A型流感病毒的11和13位密码子高度保守，在从不同宿主分离的不同甲型流感病毒感染的细胞中检测到PA-N155和PA-N182蛋白，这表明这些N-截短的PA在甲型流感病毒中的表达是普遍的。当与PB1和PB2一起表达时，这些N-截短的Pas没有表现出聚合酶活性；然而，缺乏N-截短的Pas的突变病毒在细胞培养中复制得更慢，在小鼠中的致病性比野生型病毒低。这些结果表明，这些新的PA相关蛋白可能在甲型流感病毒的复制周期中具有重要的功能。
Many replication events are involved in the influenza A virus life cycle, and they are accomplished by different virus proteins with specific functions. However, because the size of the influenza virus genome is limited, the virus uses different mechanisms to express multiple viral proteins from a single gene segment. The M2 and NS2 proteins are produced by splicing, and several novel influenza A virus proteins, such as PB1-F2, PB1-N40, and PA-X, have recently been identified. Here, we identified novel PA-related proteins in influenza A virus-infected cells. These newly identified proteins are translated from the 11th and 13th inframe AUG codons in the PA mRNA and are, therefore, N-terminally truncated forms of PA, which we named PA-N155 and PA-N182, respectively. The 11th and 13th AUG codons are highly conserved among influenza A viruses, and the PA-N155 and PA-N182 proteins were detected in cells infected with various influenza A viruses isolated from different host species, suggesting the expression of these N-truncated PAs is universal in nature among influenza A viruses. These N-truncated PAs did not show polymerase activity when expressed together with PB1 and PB2; however, mutant viruses lacking the N-truncated PAs replicated more slowly in cell culture and had lower pathogenicity in mice than did wild-type virus. These results suggest that these novel PA-related proteins likely possess important functions in the replication cycle of influenza A virus.