Characterization of human immunodeficiency virus type 1 (HIV-1) envelope variation and neutralizing antibody responses during transmission of HIV-1 subtype B

Abstract

We analyzed neutralization sensitivity and genetic variation of transmitted subtype B human immunodeficiency virus type 1 (HIV-1) in eight recently infected men who have sex with men and the virus from the six subjects who infected them. In contrast to reports of heterosexual transmission of subtype C HIV-1, in which the transmitted virus appears to be more neutralization sensitive, we demonstrate that in our study population, relatively few phenotypic changes in neutralization sensitivity or genotypic changes in envelope occurred during transmission of subtype B HIV-1. We suggest that limited genetic variation within the infecting host reduces the likelihood of selective transmission of neutralization-sensitive HIV.

FIG. 1.

Maximum-likelihood phylogenies of transmission clusters associated with chronic sources (top) and recently infected sources (bottom). Source sequences are labeled by triangles, and recipient sequences are labeled by circles. The scale bar represents genetic distance (1 = 100% divergence).

FIG. 2.

Comparison between source and recipient subjects, in terms of neutralizing antibody titers using source subject plasma (matched by transmission cluster), for infections from chronic and recently infected sources. Neutralizing antibody titers are expressed as the reciprocal of the dilution of donor plasma required to reduce the viral replication rate to 50% relative to a negative control. Boxes represent the median and interquartile ranges; whiskers extend to 1.5 times the interquartile range or the most extreme data point, whichever is closer.

FIG. 3.

Comparison between source and recipient subjects, in terms of envelope length (in amino acid residues) and potential N-linked glycosylation sites (PNGS). Boxes represent the median and interquartile ranges; whiskers extend to 1.5 times the interquartile range or the most extreme data point, whichever is closer. We also restricted analysis to the V1-V4 region, as studied by Derdeyn et al. (3); the results were comparable.