Role of seminal fluid in sexual transmission of HIV-1

This study analysed the reservoir of HIV-1 in semen and the effects of seminal plasma on the functional and phenotypic characteristics of dendritic cells (DCs), both in relation to immunoregulatory capabilities and susceptibility to infection with HIV. The reservoir of HIV-1 in semen was defined in order to assess the feasibility of 'sperm washing' as a means of reducing the risk of transmission in HTV-1-discordant couples. The fact that neither viral RNA or DNA could be detected in spermatozoa and the lack of expression of CD4 both at the protein and mRNA levels suggests that spermatozoa are not susceptible to HTV-1 infection. Viral RNA was detected in seminal plasma and both RNA and DNA were detected in non-sperm cells. As a result of this study, sperm washing is a service that is now available at the Chelsea & Westminster Hospital to HTV-l-discordant couples. This service has resulted in several births and no seroconversions in any woman who has undergone the procedure. The effects of seminal plasma on the phenotype and function of monocyte-derived DCs were investigated. Seminal plasma had suppressive effects on the allostimulatory capacity of DCs and such effects appeared to be due to down- regulation of co-stimulatory molecule expression on these cells. The suppressive effect of seminal plasma was abrogated by the removal of lipids. However, prostaglandins on their own did not have suppressive effects on DC function, suggesting that other seminal components are required to induce theobserved induction of suppression. The suppressive effect of seminal plasma on the allostimulatory function of DCs was overcome with TNF-a, as did the presence of HIV. The expression of HIV co-receptors was assessed on DCs. TNF-a induced maturation of DCs as demonstrated by reduced expression of CCR5 and increased CXCR4. Seminal plasma also enhanced expression of CXCR4 and infection with X4 strains of HIV, but down-regulated CCR5 expression and infection with R5 strains of HIV. Therefore, the regulation of co-receptor expression by DCs was associated with their susceptibility to infection with a HIV strain displaying the corresponding co-receptor usage. In summary, semen is an important vehicle for transmission of HIV. Seminal plasma was demonstrated to have profound effects on DC phenotype, maturation and function. Such alterations would influence the outcome, in terms of HIV transmission, of the interaction between the DC and HIV-1 at the mucosal surface.