An interferon lambda 4-associated variant in the hepatitis C virus RNA polymerase affects viral replication in infected cells.
An interferon lambda 4-associated variant in the hepatitis C virus RNA polymerase affects viral replication in infected cells.
复制标题
丙型肝炎病毒RNA聚合酶中的干扰素lambda 4相关变异会影响感染细胞中的病毒复制。
DOI：
10.1099/jgv.0.001495
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
McLauchlan J
中科院分区：
文献类型：
--
作者：
Bamford CGG;McLauchlan J
宿主IFNL4单倍型状态有助于急性感染丙型肝炎病毒（HCV）的个体发生慢性HCV感染。计算机模拟研究显示，HCV多聚蛋白多个位点的特定氨基酸变异与IFNL4基因座的功能性单核苷酸多态性（SNP）相关。因此，IFNL4基因座的SNP可以选择影响病毒复制的变体，从而影响感染的结果。在这里，我们研究了最显着的IFNL4相关的氨基酸变异，位于'λ（L）2环'的HCV NS5B RNA聚合酶。将L2环变体引入HCV的亚基因组复制子和全长感染性克隆中，并在存在和不存在外源IFNλ4的情况下检查病毒复制。我们的数据表明，虽然NS5B L2环的突变影响复制，但在存在和不存在IFNλ4的情况下，单个IFN λ 4相关变体对复制具有适度但一致的影响。考虑到这些变体与IFN λ 4之间的强遗传关联，这些数据表明每个个体位置对病毒复制的细微影响，其组合效应可能介导对IFNλ4作用的抗性。
Host IFNL4 haplotype status contributes to the development of chronic hepatitis C virus (HCV) infection in individuals who are acutely infected with the virus. In silico studies revealed that specific amino acid variants at multiple sites on the HCV polyprotein correlate with functional single-nucleotide polymorphisms (SNPs) in the IFNL4 locus. Thus, SNPs at the IFNL4 locus may select variants that influence virus replication and thereby the outcome of infection. Here, we examine the most significantly IFNL4-associated amino acid variants that lie in the ‘lambda (L) 2 loop’ of the HCV NS5B RNA polymerase. L2 loop variants were introduced into both sub-genomic replicon and full-length infectious clones of HCV and viral replication was examined in the presence and absence of exogenous IFNλ4. Our data demonstrate that while mutation of the NS5B L2 loop affects replication, individual IFNL4-associated variants have modest but consistent effects on replication in both the presence and absence of IFNλ4. Given the strong genetic association between these variants and IFNL4, these data suggest a nuanced effect of each individual position on viral replication, the combined effect of which might mediate resistance to the effects of IFNλ4.
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影响因子：
30.8
作者：
Ansari MA;Pedergnana V;L C Ip C;Magri A;Von Delft A;Bonsall D;Chaturvedi N;Bartha I;Smith D;Nicholson G;McVean G;Trebes A;Piazza P;Fellay J;Cooke G;Foster GR;STOP-HCV Consortium;Hudson E;McLauchlan J;Simmonds P;Bowden R;Klenerman P;Barnes E;Spencer CCA
通讯作者：
Spencer CCA
DOI：
10.1073/pnas.0504877103
发表时间：
2006-05-09
影响因子：
11.1
作者：
Pietschmann, Thomas;Kaul, Artur;Bartenschlager, Ralf
通讯作者：
Bartenschlager, Ralf
影响因子：
30.8
作者：
Prokunina-Olsson, Ludmila;Muchmore, Brian;Tang, Wei;Pfeiffer, Ruth M.;Park, Heiyoung;Dickensheets, Harold;Hergott, Dianna;Porter-Gill, Patricia;Mumy, Adam;Kohaar, Indu;Chen, Sabrina;Brand, Nathan;Tarway, McAnthony;Liu, Luyang;Sheikh, Faruk;Astemborski, Jacquie;Bonkovsky, Herbert L.;Edlin, Brian R.;Howell, Charles D.;Morgan, Timothy R.;Thomas, David L.;Rehermann, Barbara;Donnelly, Raymond P.;O'Brien, Thomas R.
通讯作者：
O'Brien, Thomas R.
DOI：
10.1073/pnas.96.23.13034
发表时间：
1999-11-09
影响因子：
11.1
作者：
Bressanelli, S;Tomei, L;Rey, FA
通讯作者：
Rey, FA
影响因子：
4.8
作者：
Ben Ouirane, Kaouther;Boulard, Yves;Bressanelli, Stephane
通讯作者：
Bressanelli, Stephane