Yanagi M, Purcell R H, Emerson S U, Bukh J
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
Virology. 1999 Sep 15;262(1):250-63. doi: 10.1006/viro.1999.9889.
Of the six major genotypes of hepatitis C virus (HCV), infectious cDNA clones of only genotype 1 have been reported. Here, we report the construction of an infectious cDNA clone representing a second major HCV genotype, genotype 2. This infectious clone (pJ6CF) encodes the consensus polyprotein of strain HC-J6(CH), genotype 2a. Its encoded polyprotein differs from those of the infectious clones of genotypes 1a and 1b by approximately 30%. Intertypic chimeric cDNA clones constructed from infectious clones of genotypes 1a and 2a of HCV were not infectious. RNA transcripts of four chimeras containing the 2a structural genes (C, E1, and E2) in the backbone of an infectious genotype 1a clone (pCV-H77C) were not viable in a chimpanzee regardless of whether p7 was from the 1a or 2a clone. However, the chimpanzee was subsequently infected with RNA transcripts of each of the two infectious parent clones, indicating that the inability of the chimeras to replicate was intrinsic to the clones and not the result of preexisting protective immune responses.
在丙型肝炎病毒（HCV）的六种主要基因型中，仅报道了基因型1的感染性cDNA克隆。在此，我们报告了代表第二种主要HCV基因型即基因型2的感染性cDNA克隆的构建。这个感染性克隆（pJ6CF）编码2a基因型HC-J6(CH)株的共有多聚蛋白。其编码的多聚蛋白与基因型1a和1b的感染性克隆的多聚蛋白大约有30%的差异。由HCV基因型1a和2a的感染性克隆构建的型间嵌合cDNA克隆没有感染性。在感染性基因型1a克隆（pCV-H77C）骨架中包含2a结构基因（C、E1和E2）的四个嵌合体的RNA转录本在黑猩猩中无法存活，无论p7是来自1a克隆还是2a克隆。然而，这只黑猩猩随后被两个感染性亲代克隆各自的RNA转录本感染，这表明嵌合体无法复制是克隆本身的内在问题，而不是预先存在的保护性免疫反应的结果。
