THE NEF GENE FROM A LONG-TERM HIV TYPE-1 NONPROGRESSOR

We examined the nef gene of HIV-I in a long-term nonprogressor to look for evidence suggesting an attenuated virus. The nef gene was previou sly shown to be required for induction of AIDS, Simian immunodeficienc y virus (SIV) deleted in nef, while infectious, fails to sustain the h igh viral loads necessary for the induction of AIDS in infected adult rhesus monkeys, The human subject of this report was found to harbor v irus (HIV-1 Sur25) encoding open-nef reading frames, However, the nef genes of this subject bore a signature point mutation: a cysteine at a mino acid 138, The sequence at this position was identical in all clon es examined over a 3-year period, When this sequence was compared to t he sequence database for AIDS and human retroviruses at Los Alamos, Ne w Mexico several isolates from other asymptomatic individuals were als o found to encode nef genes with a cysteine at position 138. Furthermo re, Cys-138 was found in chimpanzee immunodeficiency virus (CIV), a le ntivirus that is similar to HIV but does not cause AIDS in chimpanzees , Multiple cysteines are also found in the nef gene of African green m onkey virus, SVIagm, including cysteine at the position analogous to C ys-138. While seroprevalence of SIVagm is high in the wild, there is n o known disease associated with this virus, The pathogenic virus isola ted from Asian macaques, SIVmac, encodes a Nef protein that has few cy steines, Although the virus HIVSur25 encodes a completely open-nef gen e, the virus from this individual is similar to attenuated SIVmac (SIV mac239/nef-deletion) as well as HIV deleted in nef in its growth prope rties in H9 cells. Nef containing a cysteine at position 138 was shown to be responsible for determining the ability to grow in H9.