Objectives: Semen composition is influenced by HIV-1 infection, yet the impact of semen components on HIV infection of primary target cells has only been studied in samples from HIV-uninfected donors.
Design: We compared the effect of seminal plasma (SP) from chronically HIV-infected (SP+) versus uninfected donors (SP-) on HIV-1 infection of peripheral blood mononuclear cells (PBMCs) and CD4 T cells.
Methods: Primary cells were infected with HIV-1 in the presence of SP+ or SP- and analyzed for infection level, metabolic activity, HIV receptor expression, proliferation and activation. SP+ and SP- were compared for infection-enhancing peptides, cytokines and prostaglandin E2 levels.
Results: SP- efficiently enhanced HIV-1 R5 infection of CD4 T cells, whereas SP+ enhancing activity was significantly reduced. RANTES (CCL5) concentrations were elevated in SP+ relative to SP-, whereas the concentrations of infectivity-enhancing peptides [semen-derived enhancer of viral infection (SEVI), SEM1, SEM2] were similar. CCR5 membrane expression levels were reduced on CD4 T cells shortly postexposure to SP+ compared with SP- and correlated to R5-tropic HIV-1 infection levels, and CCR5 ligands' concentrations in semen. SP+ and SP- displayed similar enhancing activity on PBMC infection by X4-tropic HIV-1. Addition/depletion of RANTES (regulated on activation, normal T-cell expressed and secreted) from SPs modulated their effect on PBMC infection by R5-tropic HIV-1.
Conclusion: Semen from HIV-infected donors exhibits a significantly reduced enhancing potential on CD4 T-cell infection by R5-tropic HIV-1 when compared with semen from uninfected donors. Our data indicate that elevated seminal concentrations of RANTES in HIV-infected men can influence the ability of semen to enhance infection.