INFECTIOUS MUTANTS OF HTLV-III WITH CHANGES IN THE 3' REGION AND MARKEDLY REDUCED CYTOPATHIC EFFECTS
INFECTIOUS MUTANTS OF HTLV-III WITH CHANGES IN THE 3' REGION AND MARKEDLY REDUCED CYTOPATHIC EFFECTS
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DOI：
10.1126/science.3014663
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发表时间：
1986-08-08
期刊：
影响因子：
56.9
通讯作者：
WONGSTAAL, F
中科院分区：
文献类型：
--
作者：
FISHER, AG;RATNER, L;WONGSTAAL, F
描述了人嗜T淋巴细胞病毒III型（HTLV-III）的变体，其在体外复制但不杀死正常人T细胞。该变体命名为X10-1，通过切除病毒3“区域中跨越env和3”-orf基因的200个碱基对片段，从致细胞病变HTLV-III克隆（pHXB 2D）的基因组中衍生而来。相比之下，仅在3“-ORF中缺失55至109个碱基对的类似变体产生了极其致细胞病变的病毒。基于这些发现，可以得出结论，3“-orf基因对于HTLV-III的致细胞病变性或复制不是必需的。此外，结果表明，病毒复制和细胞毒性不是内在耦合的。此外，由于克隆X10-1保留了反式激活与病毒长末端重复序列连接的基因的能力，反式激活本身并不负责HTLV-III的T细胞杀伤。这些结果也提高了HTLV-III包膜基因的羧基末端在该病毒杀死T细胞中具有直接作用的可能性。
A variant of human T-lymphotropic virus type III (HTLV-III) is described that replicates but does not kill normal human T cells in vitro. This variant, designated X10-1, was derived from the genome of a cytopathic HTLV-III clone (pHXB2D) by excision of a 200-base pair segment in the 3'' region of the virus, spanning the env and 3''-orf genes. Comparable variants with 55 to 109 base pairs deleted exclusively in 3''-orf produced, in contrast, virus that was extremely cytopathic. On the basis of these findings it is concluded that the 3''-orf gene is not required for cytopathogenicity or replication of HTLV-III. In addition, the results suggest that virus replication and cytotoxicity are not intrinsically coupled. Furthermore, since clone X10-1 retains the ability to trnas-activate genes linked to the viral long terminal repeats, trans-activation per se is not responsible for T-cell killing by HTLV-III. These results also raise the possibility that the carboxyl terminus of the envelope gene of HTLV-III has a direct role in T-cell killing by this virus.