Full-length human immunodeficiency virus type 1 genomes from subtype C-infected seroconverters in India, with evidence of intersubtype recombination

The development of an effective human immunodeficiency virus type I (HIV-1) vaccine is likely to depend on knowledge of circulating variants of genes other than the commonly sequenced gag and env genes. In addition, full-geno me data are particularly limited for HIV-1 subtype C, currently the most co mmonly transmitted subtype in India and worldwide. Like,,ise, little is kno wn about sequence variation of HIV-1 in India, the country facing the large st burden of HIV worldwide, Therefore, the objective of this study was to c lone and characterize the complete genome of HIV-1 from seroconverters infe cted with subtype C variants in India. Cocultured HIV-1 isolates were obtai ned from six seroincident individuals from Pune, India, and virtually full- length EIN-I genomes were amplified, cloned, and sequenced from each. Seque nce analysis revealed that five of the six genomes were of subtype C, while one was a mosaic of subtypes A and C, with multiple breakpoints in env, ne f, and the 3' long terminal repeat as determined by both maximal chi(2) ana lysis and phylogenetic bootstrapping. Sequences were compared for preservat ion of known cytotoxic T lymphocyte (CTL) epitopes. Compared with those of the HIV-I, sequence, 38% of well-defined CTL epitopes were identical. The p roportion of nonconservative substitutions for Env, at 61%, was higher (P < 0.001) than those for Gag (24%), Pol (18%), and Nef (32%). Therefore, char acterized CTL epitopes demonstrated substantial differences from subtype B laboratory strains, which were most pronounced in Env, Because these clones were obtained from Indian seroconverters, they are likely to facilitate va ccine-related efforts in India by providing potential antigens for vaccine candidates as well as for assays of vaccine responsiveness.