Fisher A G, Ratner L, Mitsuya H, Marselle L M, Harper M E, Broder S, Gallo R C, Wong-Staal F
Science. 1986 Aug 8;233(4764):655-9. doi: 10.1126/science.3014663.
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 trans-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.
描述了一种人类III型嗜T淋巴细胞病毒（HTLV-III）变体，该变体在体外可复制但不杀死正常人T细胞。这种变体命名为X10-1，是通过切除病毒3'区域中跨越env和3'-orf基因的一段200个碱基对的片段，从细胞病变性HTLV-III克隆（pHXB2D）的基因组衍生而来。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的病毒具有极强的细胞病变性。基于这些发现得出结论，3'-orf基因对于HTLV-III的细胞致病性或复制并非必需。此外，结果表明病毒复制和细胞毒性并非内在相关。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相连基因的能力，因此反式激活本身并非HTLV-III杀死T细胞的原因。这些结果还增加了一种可能性，即HTLV-III包膜基因的羧基末端在该病毒杀死T细胞过程中具有直接作用。
