10月16日，國際學術期刊Virology在線發表了中國科學院上海巴斯德研究所豐田哲也研究組最新研究成果，揭示了流感病毒基因組C4啟動子/複製起點具有較弱的聚合酶識別活性，從而減弱了流感病毒的轉錄和複製。
流感病毒基因組具有8個負鏈RNA片段。在自然情況下，甲型流感病毒基因組片段3』末端第四位存在U(U4)或C(C4)的變異。博士研究生蔣紅兵等在豐田哲也的指導下，通過深入分析並比較了U4和C4啟動子/複製起點的活性差異，發現C4的複製子活性只有U4的28%。他們利用純化的流感病毒RNA聚合酶在體外分別比較了它以U4 [v84(U4)]、C4 [v84(C4)]和互補RNA鏈（c84）為模板的轉錄和複製活性差異。實驗結果表明，無論是複製還是轉錄，U4的活性都要比C4高。進一步研究發現，U4和C4啟動子/複製起點的活性差異主要來自於聚合酶對兩種不同的啟動子/複製起點識別結合活性差異。此外，他們還構建了8個基因組片段全部突變為U4或C4啟動子/複製起點的突變體流感病毒，並檢測了它們在細胞內的生長活力差異和在老鼠體內的致病力差異。實驗表明，U4突變體病毒在細胞上的生長活力增強；而C4突變體病毒在細胞上的生長活力則減弱了。但U4或C4突變體病毒在老鼠體內的致病性卻都低於野生型WSN病毒。
上述研究結果為監測、分析流感病毒的毒力以及製備流感減毒活疫苗提供了新的思路。
該研究得到了中國科學院、國家自然科學基金、李嘉誠基金會、RESPARI項目和歐盟第六框架項目(FLUINNATE)的資助。（生物谷Bioon.com）
生物谷推薦英文摘要：
Virology doi:10.1016/j.virol.2010.09.022
Influenza virus genome C4 promoter/origin attenuates its transcription and replication activity by the low polymerase recognition activity
Hongbing Jiang1, a, Shijian Zhang1, a, Qiang Wanga, Jinlan Wanga, Liqing Genga and Tetsuya Toyoda, a,
a Unit of Viral Genome Regulation, Institut Pasteur of Shanghai, Key Laboratory of Molecular Virology & Immunology, Chinese Academy of Sciences, 411 Hefei Road, Shanghai 200025, PR China
A natural variation is observed at position 4 of the 3′-end of influenza A virus genomes, where U (U4) or C (C4) is present. The replicon activity of C4 was 28% of U4. We compared the transcription and replication activity of U4 [v84(U4)], C4 [v84(C4)] and the complimentary RNA (c84) using the purified influenza virus RNA polymerase in vitro. ApG-primed replication activities of v84(C4) and c84 were 23.8% and 7.8% of v84(U4). Globin mRNA-primed transcription activities of v84(C4) and c84 were 36.9% and 6.81% of v84(U4). De novo replication activities of v84(C4) and c84 were 21.3 and 10.2% of v84(U4). This difference came from their polymerase binding activity. When all the eight genome segments of WSN strain were changed to U4, the virus titer was 760 times higher than the wild type. However, its pathogenicity in mice was lower than the wild type.