Substitution of amino acid residue V1213 in the helicase domain of the genotype 3 hepatitis E virus reduces virus replication.
Substitution of amino acid residue V1213 in the helicase domain of the genotype 3 hepatitis E virus reduces virus replication.
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DOI：
10.1186/s12985-018-0943-5
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发表时间：
2018-02-08
期刊：
影响因子：
4.8
通讯作者：
Meng XJ
中科院分区：
文献类型：
--
作者：
Cao D;Ni YY;Meng XJ
基因3型戊型肝炎病毒（HEV）感染通常与轻度疾病相关。然而，最近从重症肝炎患者中鉴定出8株基因3型HEV分离株。重要的是，这些基因3型分离株中的三个突变（S605P， I978V和V1213A）被发现是基因4型HEV的典型突变，而基因4型HEV有时与更严重的肝炎有关。因此，在这项研究中，我们试图确定这些独特的突变是否有助于增强病毒复制，从而可能导致严重的疾病。在缺乏有效的细胞培养系统来研究突变对HEV复制的影响的情况下，我们开发了一个以Renilla荧光素酶（Rluc）为报告基因的3型HEV复制子，随后用它构建了许多突变体，包括swMu-1 （V1213A）、swMu-2 （Q1246H）、swMu-3 （V1213A和Q1246H）、swMu-4 （S605P和I978V）和swMu-5 （V1213A、S605P和I978V）。将突变复制子的RNA转录物转染到Huh7 S10-3肝细胞中，以测量突变对HEV复制效率的影响。结果表明，与其他突变体相比，V1213A突变体的HEV复制效率降低幅度最大。V1213A和S605P + I978V突变对HEV复制具有累积效应，如果不是协同效应的话。与野生型HEV Rluc复制子相比，Q1246H突变体降低了HEV复制，但比V1213A突变体复制得更好。氨基酸残基V1213有利于基因3型和基因4型HEV株的复制，而不利于基因1型HEV株的复制。结果表明，V1213A突变减少了HEV复制，但可能与含有该突变的基因3型HEV分离株引起的报道的严重肝炎无关。
Genotype 3 hepatitis E virus (HEV) infection is generally associated with mild disease. However, recently eight genotype 3 HEV isolates were identified from patients with severe hepatitis. Importantly, three mutations (S605P, I978V and V1213A) in these genotype 3 isolates were found to be typical of genotype 4 HEV, which is sometime associated with more severe hepatitis. Therefore in this study we seek to determine if these unique mutations contribute to enhanced virus replication and thus potentially severe disease. In the lack of an efficient cell culture system to study the effect of mutations on HEV replication, we developed a genotype 3 HEV replicon with Renilla luciferase (Rluc) as reporter and subsequently used it to construct numerous mutants, including swMu-1 (V1213A), swMu-2 (Q1246H), swMu-3 (V1213A and Q1246H), swMu-4 (S605P and I978V), and swMu-5 (V1213A, S605P and I978V). RNA transcripts from mutant replicons were transfected into Huh7 S10–3 liver cells to measure the effect of mutations on HEV replication efficiency. The results showed that the V1213A mutant had the highest reduction in HEV replication efficiency than other mutants. The V1213A and S605P + I978V mutations have a cumulative, if not synergistic, effect on HEV replication. The Q1246H mutant decreased HEV replication compared to the wild-type HEV Rluc replicon but replicated better than the V1213A mutant. The amino acid residue V1213 favors the replication of both genotypes 3 and 4 HEV strains, but not genotype 1 HEV. The results suggested that the V1213A mutation reduced HEV replication, but is likely not associated with the reported severe hepatitis caused by genotype 3 HEV isolates containing this mutation.
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影响因子：
3.3
作者：
Meng XJ
通讯作者：
Meng XJ
DOI：
10.1111/liv.12629
发表时间：
2015-04
期刊：
Liver international : official journal of the International Association for the Study of the Liver
影响因子：
--
作者：
Smith DB;Simmonds P
通讯作者：
Simmonds P
影响因子：
5.4
作者：
Pudupakam, R. S.;Huang, Y. W.;Meng, X. J.
通讯作者：
Meng, X. J.
影响因子：
11.8
作者：
Takahashi, Kazuaki;Okamoto, Hiroaki;Mishiro, Shunji
通讯作者：
Mishiro, Shunji
DOI：
10.1099/vir.0.068429-0
发表时间：
2014-10
期刊：
The Journal of general virology
影响因子：
--
作者：
Smith DB;Simmonds P;Members Of The International Committee On The Taxonomy Of Viruses Study Group;Jameel S;Emerson SU;Harrison TJ;Meng XJ;Okamoto H;Van der Poel WHM;Purdy MA
通讯作者：
Purdy MA