THE SOR GENE OF HIV-1 IS REQUIRED FOR EFFICIENT VIRUS TRANSMISSION INVITRO
THE SOR GENE OF HIV-1 IS REQUIRED FOR EFFICIENT VIRUS TRANSMISSION INVITRO
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DOI：
10.1126/science.3497453
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发表时间：
1987-08-21
期刊：
影响因子：
56.9
通讯作者：
WONGSTAAL, F
中科院分区：
文献类型：
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作者：
FISHER, AG;ENSOLI, B;WONGSTAAL, F
人类免疫缺陷病毒HIV-1的基因组包含至少八个基因，其中三个（sor、R和3''orf）没有已知的功能。在这项研究中，通过构建一系列 HIV-1 的原病毒基因组来检查 sor 基因的作用，这些基因组要么缺乏 sor 的编码序列，要么含有 sor 的点突变。对四个此类突变体的分析表明，尽管每个克隆在转染后都可以产生形态正常的病毒颗粒，但突变体病毒建立稳定感染的能力受到限制。用sor突变体原病毒DNA转染Cos-1细胞(OKT4-)产生的病毒在无细胞条件下抵抗传播至OKT4+“易感”细胞，并且通过共培养传播得很差。相比之下，源自具有完整sor框架的克隆的病毒很容易通过任一方法繁殖。所有四种突变体均产生正常量的gag-、env-和pol衍生蛋白，并且在淋巴和非淋巴细胞中的测定表明它们的反式激活能力是完整的并且与野生型相当。因此，sor 基因虽然不是 HIV 病毒颗粒形成所必需的，但它影响病毒的体外传播，并且对于感染性病毒的有效生成至关重要。数据还表明，sor 在一个新的翻译后阶段影响病毒复制，并且其作用独立于调控基因 tat 和 trs。
The genome of the human immunodeficiency virus HIV-1 contains at least eight genes, of which three (sor, R, and 3'' orf) have no known function. In this study, the role of the sor gene was examined by constructing a series of proviral genomes of HIV-1 that either lacked the coding sequences for sor or contained point mutations in sor. Analysis of four such mutants revealed that although each clone could generate morphologically normal virus particles upon transfection, the mutant viruses were limited in their capacity to establish stable infection. Virus derived from transfection of Cos-1 cells (OKT4-) with sor mutant proviral DNA''s was resistant to transmission to OKT4+ "susceptible" cells under cell-free conditions, and was transmitted poorly by coculture. In contrast, virus derived from clones with an intact sor frame was readily propagated by either approach. Normal amounts of gag-, env-, and pol-derived proteins were produced by all four mutants and assays in both lymphoid and nonlymphoid cells indicated that their trans-activating capacity was intact and comparable with wild type. Thus the sor gene, although not absolutely required in HIV virion formation, influences virus transmission in vitro and is crucial in the efficient generation of infectious virus. The data also suggest that sor influences virus replication at a novel, post-translational stage and that its action is independent of the regulatory genses tat and trs.