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. 2012 Jun 25:9:54.
doi: 10.1186/1742-4690-9-54.

Application of a case-control study design to investigate genotypic signatures of HIV-1 transmission

Talia M Mota  1 , John M Murray, Rob J Center, Damian F J Purcell, James M McCaw
Affiliations

Application of a case-control study design to investigate genotypic signatures of HIV-1 transmission

Talia M Mota et al. Retrovirology. .

Abstract

Background: 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. 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.

Results: Subtype 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.

Conclusions: Although 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.

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Figures

Figure 1
Figure 1
Box plots displaying amino acid length of each loop between chronic sequences and transmission strains.
Figure 2
Figure 2
Case and Control Selection.
Figure 3
Figure 3
Histograms of baseline frequencies of the number of glycosites in each variable loop (for subtype-specific characteristics, see Additional file 2: Table S2).
See this image and copyright information in PMC

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