Braaten D, Franke E K, Luban J
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
J Virol. 1996 Jul;70(7):4220-7. doi: 10.1128/JVI.70.7.4220-4227.1996.
The human immunodeficiency virus type 1 (HIV-1) Gag polyprotein binds to cyclophilin A and incorporates this cellular peptidyl prolyl-isomerase into virions. Disruption of cyclophilin A incorporation, either by gag mutations or by cyclosporine A, inhibits virion infectivity, indicating that cyclophilin A plays an essential role in the HIV-1 life cycle. Using assays for packaging of cyclophilin A into virions and for viral replication sensitivity to cyclosporine A, as well as information gleaned from the alignment of Gag residues encoded by representative viral isolates, we demonstrate that of the five lineages of primate immunodeficiency viruses, only HIV-1 requires cyclophilin A for replication. Cloned viral isolates from clades A, B, and D of HIV-1 group M, as well as a phylogenetically related isolate from chimpanzee, all require cyclophilin A for replication. In contrast, the replication of two outlier (group O) HIV-1 isolates is unaffected by concentrations of cyclosporine A which disrupt cyclophilin A incorporation into virions, indicating that these viruses are capable of replicating independently of cyclophilin A. These studies identify the first phenotypic difference between HIV-1 group M and group O and are consistent with phylogenetic studies suggesting that the two HIV-1 groups were introduced into human populations via separate zoonotic transmission events.
1型人类免疫缺陷病毒（HIV-1）的Gag多聚蛋白与亲环素A结合，并将这种细胞肽基脯氨酰异构酶纳入病毒颗粒。通过gag突变或环孢素A破坏亲环素A的纳入，会抑制病毒颗粒的感染性，这表明亲环素A在HIV-1生命周期中起重要作用。利用将亲环素A包装到病毒颗粒中的检测方法以及病毒复制对环孢素A的敏感性，再结合从代表性病毒分离株编码的Gag残基比对中收集到的信息，我们证明在灵长类免疫缺陷病毒的五个谱系中，只有HIV-1需要亲环素A进行复制。从HIV-1 M组的A、B和D分支克隆的病毒分离株，以及来自黑猩猩的一个系统发育相关分离株，都需要亲环素A进行复制。相比之下，两种异常（O组）HIV-1分离株的复制不受破坏亲环素A纳入病毒颗粒的环孢素A浓度的影响，这表明这些病毒能够独立于亲环素A进行复制。这些研究确定了HIV-1 M组和O组之间的首个表型差异，并且与系统发育研究一致，表明这两个HIV-1组是通过不同的人畜共患病传播事件引入人类群体的。
