In vivo analysis of the 3′ untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone
In vivo analysis of the 3′ untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone
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DOI：
10.1073/pnas.96.5.2291
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Bukh, J
中科院分区：
文献类型：
--
作者：
Yanagi, M;St Claire, M;Bukh, J
从感染性cDNA克隆中删除了丙型肝炎病毒（HCV） 3'非翻译区（UTR）的大部分片段，并对7个缺失突变体的RNA转录物在黑猩猩中的传染性进行了顺序测试。缺乏全部或部分3'末端保守区或多聚（U-UC）区域的突变体无法感染黑猩猩，这表明这两个区域对体内传染性至关重要。然而，第三个区域，即可变区域，能够容忍破坏该区域内两个假定的茎环结构的缺失。含有3' UTR可变区近24 nt缺失的突变体VR-24在黑猩猩中是可行的，并且似乎与未缺失的亲本病毒一样可以复制。接种突变型VR-24后1周，黑猩猩出现病毒血症，在早期急性感染期间，HCV基因组滴度随着时间的推移而增加。因此，3' UTR的poly（U-UC）区和保守区（而非可变区）似乎对HCV的体内感染性至关重要。
Large sections of the 3' untranslated region (UTR) of hepatitis C virus (HCV) were deleted from an infectious cDNA clone, and the RNA transcripts from seven deletion mutants were tested sequentially for infectivity in a chimpanzee. Mutants lacking all or part of the 3' terminal conserved region or the poly(U-UC) region were unable to infect the chimpanzee, indicating that both regions are critical for infectivity in vivo. However, the third region, the variable region, was able to tolerate a deletion that destroyed the two putative stem-loop structures within this region. Mutant VR-24 containing a deletion of the proximal 24 nt of the variable region of the 3' UTR was viable in the chimpanzee and seemed to replicate as well as the undeleted parent virus. The chimpanzee became viremic 1 week after inoculation with mutant VR-24, and the HCV genome titer increased over time during the early acute infection. Therefore, the poly(U-UC) region and the conserved region, but not the variable region, of the 3' UTR seem to be critical for in vivo infectivity of HCV.