Human immunodeficiency virus type 1 env sequences from Calcutta in easternIndia: Identification of features that distinguish subtype C sequences in India from other subtype C sequences

India is experiencing a rapid spread of human immunodeficiency virus type 1 (HIV-1), primarily through heterosexual transmission of subtype C viruses. To delineate the molecular features of HIV-1 circulating in India, we sequ enced the V3-V4 region of viral env from 21 individuals attending an HIV cl inic in Calcutta, the most populous city in the eastern part of the country , and analyzed these and the other Indian sequences in the HIV database. Tw enty individuals were infected with viruses having a subtype C env, and one had viruses with a subtype A env. Analyses of 192 subtype C sequences that included one sequence for each subject from this study and from the HIV da tabase revealed that almost all sequences from India, along with a small nu mber from other countries, form a phylogenetically distinct lineage within subtype C, which we designate C-IN. Overall, C-IN lineage sequences were mo re closely related to each other (level of diversity, 10.2%) than to subtyp e C sequences from Botswana, Burundi, South Africa, Tanzania, and Zimbabwe (range, 15.3 to 20.7%). Of the three positions identified as signature amin o acid substitution sites for C-IN sequences (K340E, K350A, and G429E), 56% of the C-IN sequences contained all three amino acids while 87% of the seq uences contained at least two of these substitutions. Among the non-C-IN se quences, all three amino acids were present in 2%, while 22% contained two or more of these amino acids. These results suggest that much of the curren t Indian epidemic is descended from a single introduction into the country. Identification of conserved signature amino acid positions could assist ep idemiologic tracking and has implications for the development of a vaccine against subtype C HIV-1 in India.