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Background:  A small number of newly infected subjects with HIV-1 subtype-C viruses were shown to have significantly shorter envelope variable loops and a lower number of potential N-linked glycosylation sites than the viruses harbored by their long-term infected partners. We examined whether viruses with these characteristics were present early in infection in other HIV-1 subtypes, and whether they persist over the course of infection.

Methods:  We compared V1-V2 length and glycosylation sites for HIV-1 subtype-A and HIV-1 subtype-B sequences taken early in infection to the respective subtype sequences from the Los Alamos database, which represent all phases of infection. Changes in V1-V2 length and glycosylation sites were also examined for 9 subtype-A subjects by isolating multiple envelope sequences early and 2 to 3 years after infection.

Results:  Heterosexually acquired subtype-A viruses (n = 35), a median of 70 days post infection (IQR 50 to 151), had significantly shorter V1-V2 loop sequences (p = 0.02) and fewer glycosylation sites (p = 0.03) than subtype-A sequences from the database (n = 51). Subtype-B viruses (n = 13), a median of 142 days post infection (IQR 114 to 234) and primarily acquired through injection drug use and homosexual contact, did not have shorter or less glycosylated V1-V2 loops from the subtype-B sequences in the database (n = 154). Longitudinal analysis of 9 subjects with subtype-A infection showed that 6 of them had a significantly higher number of glycosylation sites and 3 of them had longer V1-V2 loops in the later sequences than the transmitted variants. When sequences from all 9 subjects were considered in aggregate, sequences 2 to 3 years after infection had a significantly higher number of glycosylation sites (p < 0.0001), but no significant change in V1-V2 length compared with the transmitted sequences.

Conclusions:  Heterosexually transmitted subtype-A viruses have shorter and less glycosylated envelope variable loops early in infection, but acquire glycosylation sites over the course of infection. Because of possible differences in the mode of transmission, there is no apparent selection for shorter and less glycosylated envelope variable loops in subtype-B transmissions.

Keywords: transmission; subtypes; envelope