OA21.05
Background: The global spread of HIV−1 has been fueled by sexual transmission with the epidemic disproportionately affecting men who sex with men (MSM). As the epidemic in MSM continues unabated, understanding the virus-host interactions responsible for transmission may be critical for the development of an HIV vaccine and other prevention strategies.
Methods: To elucidate the nature of the transmitted/founder (TF) virus following rectal transmission, we developed a novel analytical strategy utilizing deep sequencing data from a cohort of 67 acutely infected MSM subjects.
Results: Empirical analyses revealed that deep sequencing could not only reliably infer the TF virus but also discriminate between single and multiple HIV infections. Using this approach we found that most transmissions resulted from a single infection with only 16% of individuals exhibiting evidence of multiple variant transmissions. We extended this study to identify signature mutations that may be favored at transmission between viruses originating from heterosexual exposure versus those from MSM. Here, we focused on a comprehensive analysis of Env sequences from 125 early subjects (Fiebig I-III) to discern the genetic imprint on the underlying composition of the viral quasispecies. A number of genetic signatures were identified in gp120 and the gp41 cytoplasmic tail. One signature pattern specifically enriched in TF viruses from MSM was the loss of an N-linked glycosylation site at position 362 in the C3 region adjacent to the CD4 binding site. The loss of this glycosylation motif has previously been associated with chronic infection and implicated in increased cell-to-cell fusion activity and a high apoptosis inducing phenotype.
Conclusions: Taken together, these findings provide unique insight into the events of early transmission in MSM and reveal potentially important mechanistic differences that may exist between the different routes of sexual transmission that are not yet fully understood.
