Premkumar D R, Ma X Z, Maitra R K, Chakrabarti B K, Salkowitz J, Yen-Lieberman B, Hirsch M S, Kestler H W
Department of Molecular Biology, Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.
AIDS Res Hum Retroviruses. 1996 Mar 1;12(4):337-45. doi: 10.1089/aid.1996.12.337.
We examined the nef gene of HIV-1 in a long-term nonprogressor to look for evidence suggesting an attenuated virus. The nef gene was previously shown to be required for induction of AIDS. Simian immunodeficiency virus (SIV) deleted in nef, while infectious, fails to sustain the high viral loads necessary for the induction of AIDS in infected adult rhesus monkeys. The human subject of this report was found to harbor virus (HIV-1 Sur25) encoding open-nef reading frames. However, the nef genes of this subject bore a signature point mutation: a cysteine at amino acid 138. The sequence at this position was identical in all clones examined over a 3-year period. When this sequence was compared to the sequence database for AIDS and human retroviruses at Los Alamos, New Mexico, several isolates from other asymptomatic individuals were also found to encode nef genes with a cysteine at position 138. Furthermore, Cys-138 was found in chimpanzee immunodeficiency virus (CIV), a lentivirus that is similar to HIV but does not cause AIDS in chimpanzees. Multiple cysteines are also found in the nef gene of African green monkey virus, SVIagm, including cysteine at the position analogous to Cys-138. While seroprevalence of SIVagm is high in the wild, there is no known disease associated with this virus. The pathogenic virus isolated from Asian macaques, SIVmac, encodes a Nef protein that has few cysteines. Although the virus HIVSur25 encodes a completely open-nef gene, the virus from this individual is similar to attenuated SIVmac (SIVmac239/nef-deletion) as well as HIV deleted in nef in its growth properties in H9 cells. Nef containing a cysteine at position 138 was shown to be responsible for determining the ability to grow in H9.
我们检测了一名长期不进展者体内的HIV-1 nef基因，以寻找表明病毒减毒的证据。此前研究表明，nef基因是诱发艾滋病所必需的。猿猴免疫缺陷病毒（SIV）缺失nef基因后虽仍具传染性，但无法在受感染的成年恒河猴体内维持诱发艾滋病所需的高病毒载量。本报告中的人类受试者体内携带编码开放阅读框nef的病毒（HIV-1 Sur25）。然而，该受试者的nef基因存在一个特征性点突变：第138位氨基酸为半胱氨酸。在3年期间检测的所有克隆中，该位置的序列均相同。当将此序列与新墨西哥州洛斯阿拉莫斯的艾滋病和人类逆转录病毒序列数据库进行比对时，发现其他一些无症状个体的分离株也编码第138位为半胱氨酸的nef基因。此外，在黑猩猩免疫缺陷病毒（CIV）中也发现了Cys-138，CIV是一种与HIV相似但不会在黑猩猩中引发艾滋病的慢病毒。在非洲绿猴病毒SVIagm的nef基因中也发现了多个半胱氨酸，包括与Cys-138位置类似的半胱氨酸。虽然野生环境中SIVagm的血清阳性率很高，但尚无已知疾病与该病毒相关。从亚洲猕猴中分离出的致病病毒SIVmac编码的Nef蛋白含有的半胱氨酸很少。尽管病毒HIVSur25编码一个完全开放的nef基因，但该个体的病毒在H9细胞中的生长特性与减毒的SIVmac（SIVmac239/nef缺失）以及缺失nef的HIV相似。已证明第138位含半胱氨酸的Nef负责决定在H9细胞中的生长能力。
