Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity.
Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity.
复制标题
PA-X C 末端的 20 个氨基酸与甲型流感病毒复制和致病性增强相关
DOI：
10.1099/vir.0.000143
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Sun Y
中科院分区：
文献类型：
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作者：
Gao H;Sun H;Hu J;Qi L;Wang J;Xiong X;Wang Y;He Q;Lin Y;Kong W;Seng LG;Pu J;Chang KC;Liu X;Liu J;Sun Y
PA-X蛋白是近年来在甲型流感病毒（IAV）中发现的一种由PA翻译过程中的核糖体移码引起的蛋白。IAV中PA-X蛋白的C-末端结构域“X”可分为全长（61 aa）或截短的（41 aa）。 主要地，禽流感病毒表达全长PA-X蛋白，而2009年大流行性H1N1（pH 1 N1）流感病毒含有截短的PA蛋白。截短形式缺乏全长PA-X蛋白的aa 232-252。PA-X长度在病毒功能中的意义尚不清楚。为了解决这个问题，我们构建了一套当代流感病毒（pH 1 N1，禽H5 N1和H9 N2）与完整的和截短的PA-X通过反向遗传学比较其复制和宿主致病性。相对于相应的截短型PA-X病毒，人A549细胞中的所有全长PA-X病毒均使病毒复制增加10至100倍，并使细胞凋亡增加5- 8%。全长PA-X病毒毒性更强，在小鼠中引起更严重的炎症反应。此外，在PA-X的C末端的aa 233-252强烈抑制共转染基因的表达约50%，表明这些末端20个aa可能在增强病毒复制中起作用并有助于毒力。
The PA-X protein, arising from ribosomal frameshift during PA translation, was recently discovered in influenza A virus (IAV). The C-terminal domain ‘X’ of PA-X proteins in IAVs can be classified as full-length (61 aa) or truncated (41 aa). In the main, avian influenza viruses express full-length PA-X proteins, whilst 2009 pandemic H1N1 (pH1N1) influenza viruses harbour truncated PA proteins. The truncated form lacks aa 232–252 of the full-length PA-X protein. The significance of PA-X length in virus function remains unclear. To address this issue, we constructed a set of contemporary influenza viruses (pH1N1, avian H5N1 and H9N2) with full and truncated PA-X by reverse genetics to compare their replication and host pathogenicity. All full-length PA-X viruses in human A549 cells conferred 10- to 100-fold increase in viral replication and 5–8 % increase in apoptosis relative to corresponding truncated PA-X viruses. Full-length PA-X viruses were more virulent and caused more severe inflammatory responses in mice. Furthermore, aa 233–252 at the C terminus of PA-X strongly suppressed co-transfected gene expression by ∼50 %, suggesting that these terminal 20 aa could play a role in enhancing viral replication and contribute to virulence.