Chen S S, Ferrante A A, Terwilliger E F
Division of Hematology/Oncology, Deaconess Hospital, Boston, Massachusetts 02215, USA.
Virology. 1996 Dec 15;226(2):260-8. doi: 10.1006/viro.1996.0654.
A mutant human immunodeficiency virus (HIV-1) provirus encoding an envelope (Env) protein with a truncated transmembrane protein cytoplasmic domain was defective for replication. Coexpression of the mutant with a wild-type (wt) HIV-1 provirus potently inhibited the production of infectious virus. The maximum inhibitory effect was reached when the ratio of mutant to wt proviral DNA was 2:1. This transdominant defect in infectivity conferred by the mutant Env did not appear to involve the late steps of virus replication, since the synthesis, precursor processing, and intracellular transport of the Env proteins were not blocked; nor did it prevent the incorporation of the envelope proteins into virions or the subsequent release of the virus. Although the mutant Env protein still retained syncytia-forming ability, the truncated protein was unable to mediate cell-to-cell transmission of the virus. Moreover, coexpression with the mutant effectively inhibited the ability of the wt Env to mediate cell-to-cell transmission. The mutant Env protein formed a complex with the wt protein when they were coexpressed, producing heterooligomeric structures which appeared to be severely defective in an early, post-CD4 binding step of the virus life cycle despite the inclusion of wt Env in the complexes.
一种编码具有截短跨膜蛋白胞质结构域的包膜（Env）蛋白的突变型人类免疫缺陷病毒（HIV-1）前病毒复制存在缺陷。该突变体与野生型（wt）HIV-1前病毒共表达时能有效抑制感染性病毒的产生。当突变体与野生型前病毒DNA的比例为2:1时，达到最大抑制效果。由突变Env赋予的这种显性感染缺陷似乎不涉及病毒复制的后期步骤，因为Env蛋白的合成、前体加工和细胞内运输未被阻断；它也没有阻止包膜蛋白掺入病毒粒子或随后的病毒释放。尽管突变Env蛋白仍保留形成合胞体的能力，但截短的蛋白无法介导病毒的细胞间传播。此外，与突变体共表达有效抑制了野生型Env介导细胞间传播的能力。当突变Env蛋白与野生型蛋白共表达时，它们形成复合物，产生异源寡聚体结构，尽管复合物中包含野生型Env，但这些结构在病毒生命周期中CD4结合后的早期步骤似乎存在严重缺陷。
