Institute for Cellular and Molecular Biology, Section of Molecular Genetics and Microbiology, University of Texas at Austin, Austin, TX 78746, USA.
Virology. 2010 Dec 20;408(2):146-58. doi: 10.1016/j.virol.2010.09.012. Epub 2010 Oct 8.
We demonstrate that influenza A virus strains that circulate in humans differ markedly in the ability of their NS1 proteins to block the activation of IRF3 and interferon-β transcription. Strong activation occurs in cells infected with viruses expressing NS1 proteins of seasonal H3N2 and H2N2 viruses, whereas activation is blocked in cells infected with viruses expressing NS1 proteins of some, but not all seasonal H1N1 viruses. The NS1 proteins of the 2009 H1N1 and H5N1 viruses also block these activations. The difference in this NS1 function is mediated largely by the C-terminal region of the effector domain, which contains the only amino acid (K or E at position 196) that covaries with the functional difference. Further, we show that TRIM25 binds the NS1 protein whether or not IRF3 activation is blocked, demonstrating that binding of TRIM25 by the NS1 protein does not necessarily lead to the blocking of IRF3 activation.
我们证明，在人类中流行的甲型流感病毒株在其 NS1 蛋白阻断 IRF3 和干扰素-β转录激活的能力上有显著差异。在感染表达季节性 H3N2 和 H2N2 病毒 NS1 蛋白的细胞中会发生强烈的激活，而在感染表达某些但不是所有季节性 H1N1 病毒 NS1 蛋白的细胞中则会被阻断。2009 年 H1N1 和 H5N1 病毒的 NS1 蛋白也会阻断这些激活。这种 NS1 功能的差异主要是由效应结构域的 C 末端区域介导的，该区域包含与功能差异相关的唯一氨基酸（位置 196 处的 K 或 E）。此外，我们还表明，TRIM25 无论是否阻断 IRF3 激活都会与 NS1 蛋白结合，这表明 NS1 蛋白与 TRIM25 的结合不一定会导致 IRF3 激活的阻断。
