HIV-1 subtype C transmitted founders modulate dendritic cell inflammatory responses.

Background: Heterosexual transmission remains the main route of HIV-1 transmission and female genital tract (FGT) inflammation increases the risk of infection. However, the mechanism(s) by which inflammation facilitates infection is not fully understood. In rhesus macaques challenged with simian immunodeficiency virus, dendritic cell (DC) mediated recruitment of CD4+ T cells to the FGT was critical for infection.

Selective transmission of some HIV-1 subtype C variants might depend on Envelope stimulating dendritic cells to secrete IL-10.

Envelope (Env) phenotype(s) that provide transmitted founders (TF) with a selective advantage during HIV-1 transmission would be the ideal target for preventative therapy. We generated Env clones from four individuals infected with a single virus and one participant infected with multiple variants at transmission and compared phenotype with matched Envs from chronic infection (CI). When we determined whether pseudovirus (PSV) of the five TF and thirteen matched CI Env clones differed in their ability to 1) enter TZM-bl cells, 2) bind DC-SIGN, and 3) trans-infect CD4+ cells there was no association between time post-infection and variation in Env phenotype.

HIV-1 subtype C Envelope function becomes less sensitive to N-glycosylation deletion during disease progression.

Objective: As part of a larger study to understand how Envelope N-glycosylation influences HIV-1 pathogenesis, we selected a participant infected with a single Subtype C variant and determined whether deletion of specific potential N-glycan sites (PNGs) impacted Envelope function longitudinally.

Results: We deleted five PNGs previously linked to HIV-1 transmission of two matched Envelope clones representing variants at 5 and 173 weeks post-infection. The transmitted founder (TF) had significantly better pseudovirus entry efficiency than the chronic infection (CI) variant.