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Abstract
BackgroundThe characterization of HIV-1 transmission strains may inform the design of an effective vaccine. Shorter variable loops with fewer predicted glycosites have been suggested as signatures enriched in envelope sequences derived during acute HIV-1 infection. Specifically, a transmission-linked lack of glycosites within the V1 and V2 loops of gp120 provides greater access to an α4β7 binding motif, which promotes the establishment of infection. Also, a histidine at position 12 in the leader sequence of Env has been described as a transmission signature that is selected against during chronic infection. The purpose of this study is to measure the association of the presence of an α4β7 binding motif, the number of N-linked glycosites, the length of the variable loops, and the prevalence of histidine at position 12 with HIV-1 transmission. A case–control study design was used to measure the prevalence of these variables between subtype B and C transmission sequences and frequency-matched randomly-selected sequences derived from chronically infected controls.ResultsSubtype B transmission strains had shorter V3 regions than chronic strains (p = 0.031); subtype C transmission strains had shorter V1 loops than chronic strains (p = 0.047); subtype B transmission strains had more V3 loop glycosites (p = 0.024) than chronic strains. Further investigation showed that these statistically significant results were unlikely to be biologically meaningful. Also, there was no difference observed in the prevalence of a histidine at position 12 among transmission strains and controls of either subtype.ConclusionsAlthough a genetic bottleneck is observed after HIV-1 transmission, our results indicate that summary characteristics of Env hypothesised to be important in transmission are not divergent between transmission and chronic strains of either subtype. The success of a transmission strain to initiate infection may be a random event from the divergent pool of donor viral sequences. The characteristics explored through this study are important, but may not function as genotypic signatures of transmission as previously described.
Highlights
The characterization of Sequence Database (HIV)-1 transmission strains may inform the design of an effective vaccine
Amino acid lengths of the variable loops When measuring the amino acid (AA) lengths, only subtype C V1 loops and subtype B V3 loops were significantly different between transmission strains and chronic controls (p = 0.047; p = 0.031, respectively; Table 1)
When gp120 has access to bind α4β7, there exists a capacity for a population of CD4+ T cells to be highly susceptible to infection with HIV-1 [11,15,21,22,23]
Summary
The characterization of HIV-1 transmission strains may inform the design of an effective vaccine. Shorter variable loops with fewer predicted glycosites have been suggested as signatures enriched in envelope sequences derived during acute HIV-1 infection. A number of different approaches have been used to identify transmission signatures, investigating whether shorter variable loops with fewer predicted N-linked glycosylation sites (glycosites) are characteristics enriched in Env from viruses derived during acute infection. In ten self-reported transmission pairs of subtype B, Liu et al showed that gp120 sequences had shorter variable regions and reduced numbers of glycosites following transmission to the new host [19] They state that their results were dependent upon how pairs were chosen for inclusion, and that no other study had yet found these reductions to be measured consistently across various acute infections.
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