Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
Science. 2012 Jul 13;337(6091):199-204. doi: 10.1126/science.1222213. Epub 2012 Jun 28.
Influenza A virus (IAV) infection leads to variable and imperfectly understood pathogenicity. We report that segment 3 of the virus contains a second open reading frame ("X-ORF"), accessed via ribosomal frameshifting. The frameshift product, termed PA-X, comprises the endonuclease domain of the viral PA protein with a C-terminal domain encoded by the X-ORF and functions to repress cellular gene expression. PA-X also modulates IAV virulence in a mouse infection model, acting to decrease pathogenicity. Loss of PA-X expression leads to changes in the kinetics of the global host response, which notably includes increases in inflammatory, apoptotic, and T lymphocyte-signaling pathways. Thus, we have identified a previously unknown IAV protein that modulates the host response to infection, a finding with important implications for understanding IAV pathogenesis.
甲型流感病毒（IAV）感染导致的致病性具有变异性和不完全理解。我们报告称，病毒的第 3 个片段包含第二个开放阅读框（“X-ORF”），通过核糖体移码来访问。该移码产物被称为 PA-X，包含病毒 PA 蛋白的内切酶结构域和由 X-ORF 编码的 C 末端结构域，其功能是抑制细胞基因表达。PA-X 还在小鼠感染模型中调节 IAV 的毒力，从而降低致病性。PA-X 表达的丧失会导致宿主反应的整体动力学发生变化，这特别包括炎症、凋亡和 T 淋巴细胞信号通路的增加。因此，我们已经鉴定出一种以前未知的 IAV 蛋白，它可以调节宿主对感染的反应，这一发现对理解 IAV 发病机制具有重要意义。
