标题: [转移贴]-Science：研究者揭示A型流感基因组编码新蛋白 [打印本页] 作者: rojjer 时间: 2015-8-17 11:03 标题: [转移贴]-Science：研究者揭示A型流感基因组编码新蛋白 原帖由ipsvirus发表于2/7/2012 13:12
新的研究揭示了A型流感病毒中的一个从前未知的基因，这种病毒最常感染禽类，但也会在人类和其它哺乳动物中引起大流行。尽管科学家们对这些病毒进行了十分细致的研究，但他们仍然对病毒与其宿主间的分子相互作用了解得相对较少。这些新的发现应该能够帮助扩展对它的了解并可能提出一种有用的抗病毒疗法的标靶。Brett Jagger及其同事如今发现了隐藏在该病毒相对较小的基因组中的一个新的基因。其蛋白质是在核糖体阅读信使RNA的核苷酸链的同时向前跳过时产生的。核糖体是以三个核苷酸一组来阅读的，因此如果它向前跳过一个核苷酸的话，它会以不同的组合来阅读核苷酸。
Jagger及其同事在Science上报告说，这样一种在PA聚合酶基因内的“核糖体框架移动”产生了一种他们称之为PA-X的蛋白。这种蛋白会抑制RNA多聚酶II的表达，而该酶负责将DNA转录成为信使RNA。在感染了某种重组版本的1918年西班牙流感病毒的小鼠中，PA-X影响了细胞免疫反应所需的宿主基因的表达，表明该蛋白会影响动物中的致病过程。
转自http://www.bioon.com/biology/Microbiology/525872.shtml 作者: rojjer 时间: 2015-8-17 11:06
ipsvirus：
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.
dentification of novel influenza A virus proteins translated from PA mRNA.
Muramoto Y, Noda T, Kawakami E, Akkina R, Kawaoka Y.
Abstract
Many replication events are involved in the influenza A virus life cycle, which are accomplished by different virus proteins with specific functions. However, because the size of 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 eleventh and thirteenth in-frame 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 eleventh and thirteenth 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.