新的研究揭示了A型流感病毒中的一個(gè)從前未知的基因，這種病毒最常感染禽類,，但也會(huì)在人類和其它哺乳動(dòng)物中引起大流行。盡管科學(xué)家們對(duì)這些病毒進(jìn)行了十分細(xì)致的研究,，但他們?nèi)匀粚?duì)病毒與其宿主間的分子相互作用了解得相對(duì)較少,。這些新的發(fā)現(xiàn)應(yīng)該能夠幫助擴(kuò)展對(duì)它的了解并可能提出一種有用的抗病毒療法的標(biāo)靶。
Brett Jagger及其同事如今發(fā)現(xiàn)了隱藏在該病毒相對(duì)較小的基因組中的一個(gè)新的基因,。其蛋白質(zhì)是在核糖體閱讀信使RNA的核苷酸鏈的同時(shí)向前跳過時(shí)產(chǎn)生的,。核糖體是以三個(gè)核苷酸一組來閱讀的，因此如果它向前跳過一個(gè)核苷酸的話,，它會(huì)以不同的組合來閱讀核苷酸,。
Jagger及其同事在Science上報(bào)告說，這樣一種在PA聚合酶基因內(nèi)的“核糖體框架移動(dòng)”產(chǎn)生了一種他們稱之為PA-X的蛋白,。這種蛋白會(huì)抑制RNA多聚酶II的表達(dá),，而該酶負(fù)責(zé)將DNA轉(zhuǎn)錄成為信使RNA,。在感染了某種重組版本的1918年西班牙流感病毒的小鼠中，PA-X影響了細(xì)胞免疫反應(yīng)所需的宿主基因的表達(dá),，表明該蛋白會(huì)影響動(dòng)物中的致病過程,。（生物谷Bioon.com）
doi:10.1126/science.1222213
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An Overlapping Protein-Coding Region in Influenza A Virus Segment 3 Modulates the Host Response
B. W. Jagger1,2, H. M. Wise1,*, J. C. Kash2, K.-A. Walters3, N. M. Wills4, Y.-L. Xiao2, R. L. Dunfee2, L. M. Schwartzman2, A. Ozinsky3, G. L. Bell1,†, R. M. Dalton1,‡, A. Lo1, S. Efstathiou1, J. F. Atkins4,5, A. E. Firth1,§, J. K. Taubenberger2,§, P. Digard1,*,§
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 FS 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.
