Hepatitis C virus JFH-1 strain infection in chimpanzees is associated with low pathogenicity and emergence of an adaptive mutation.
Hepatitis C virus JFH-1 strain infection in chimpanzees is associated with low pathogenicity and emergence of an adaptive mutation.
复制标题
黑猩猩中的丙型肝炎病毒JFH-1菌株感染与低致病性和自适应突变的出现有关。
DOI：
10.1002/hep.22422
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发表时间：
2008-09
期刊：
影响因子：
13.5
通讯作者：
Liang, T. Jake
中科院分区：
文献类型：
--
作者：
Kato, Takanobu;Choi, Youkyung;Elmowalid, Gamal;Sapp, Ronda K.;Barth, Heidi;Furusaka, Akihiro;Mishiro, Shunji;Wakita, Takaji;Krawczynski, Krzysztof;Liang, T. Jake
丙型肝炎病毒JFH-1株的鉴定使感染性细胞培养系统的成功开发成为可能。虽然该菌株在细胞培养中能高效复制并产生感染性病毒，但其体内复制能力和致病机制尚不清楚。为了评估JFH-1病毒的体内表型，将细胞培养产生的JFH-1病毒(JFH-1CC)和从其分离的JFH-1患者血清接种到黑猩猩体内。两只动物在接种后3天都呈丙型肝炎病毒RNA阳性，但表现出低水平的病毒血症，没有肝炎的证据。在JFH-1CC和患者血清感染的黑猩猩中，丙型肝炎病毒血症分别持续8周和34周。免疫学分析表明，在两种动物中都诱导了类似的丙型肝炎病毒特异性免疫反应。对感染不同时间点的丙型肝炎病毒的测序显示，在接受患者血清接种的黑猩猩中，有更多的替换，较高水平的序列变异似乎与这种动物的长期感染有关。在这两只黑猩猩中，NS2区域的一个共同突变G838R很早就出现了。这种突变增强了病毒的组装，导致转基因或感染细胞中病毒产量的增加。我们的研究表明，丙型肝炎病毒JFH-1株对黑猩猩的感染减弱，致病性低，并能够在体内适应独特的突变，从而增强复制表型。
The identification of the hepatitis C virus (HCV) strain JFH-1 enabled the successful development of infectious cell culture systems. Although this strain replicates efficiently and produces infectious virus in cell culture, the replication capacity and pathogenesis in vivo are still undefined. To assess the in vivo phenotype of the JFH-1 virus, cell culture-generated JFH-1 virus (JFH-1cc) and patient serum from which JFH-1 was isolated were inoculated into chimpanzees. Both animals became HCV RNA-positive 3 days after inoculation, but showed low-level viremia and no evidence of hepatitis. HCV viremia persisted 8 and 34 weeks in JFH-1cc and patient serum-infected chimpanzees, respectively. Immunological analysis revealed that HCV-specific immune responses were similarly induced in both animals. Sequencing of HCV at various time points of infection revealed more substitutions in the patient serum-inoculated chimpanzee and the higher level of sequence variations seemed to be associated with a prolonged infection in this animal. A common mutation G838R in the NS2 region emerged early in both chimpanzees. This mutation enhances viral assembly leading to an increase in viral production in transfected or infected cells. our study shows that the HCV JFH-1 strain causes attenuated infection and low pathogenicity in chimpanzees, and is capable of adapting in vivo with a unique mutation conferring enhanced replicative phenotype.
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影响因子：
13.5
作者：
Beard, MR;Abell, G;Lemon, SM
通讯作者：
Lemon, SM
影响因子：
3.7
作者：
Hong, Z;Beaudet-Miller, M;Lau, JYN
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影响因子：
5.4
作者：
Kato, Takanobu;Matsumura, Takuya;Liang, T. Jake
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Liang, T. Jake
影响因子：
14.8
作者：
Kato, Takanobu;Date, Tomoko;Wakita, Takaji
通讯作者：
Wakita, Takaji
影响因子：
5.4
作者：
Major, ME;Mihalik, K;Feinstone, SM
通讯作者：
Feinstone, SM