Sequences and phylogenetic analysis of the nef gene from Thai subjects harboring subtype E HIV-1

It has been demonstrated that nef-defective SIV can cause attenuated disease in rhesus monkeys and that animals immunized with a similar construct can be protected when challenged with wild-type, pathogenic SIV. This finding has sparked interest in the nef gene of HIV-1. It remains unclear, however, whether nef serves an analogous role in human HIV-1 infection; Deacon et al. have reported an association of deletions in the nef gene with an attenuated disease course in humans, although other work does not support a strict correlation between the structure or function of nef and rates of disease progression. The nef gene product has been shown to influence the infectivity and pathogenicity of HIV-1. nef may also have a role in the immune response to HIV-1. The current database of nef sequences is derived almost exclusively from subtype B viruses. The authors therefore sought to develop a database of nef sequences from subjects infected with HIV-1 subtype E. Whole-blood samples were collected from 103 male commercial sex workers in Chiang Mai, Thailand. 17 tested positive for infection with HIV-1, 16 of whom were infected with subtype E by gp120 characterization. Intersubject variation in subtype E nef genes at the nucleotide level ranged from 2.1-7.8%. Thai subtype E nef sequences are more tightly clustered than subtype B nef sequences, analogous to what is seen in env. The authors note that their subtype E nef sequences do not share the genotypic polymorphism in the area of residues 10-30 noted with subtype B nef. These data confirm the need to develop a set of subtype E-specific reagents.