Background: Trichomoniasis caused by the genitourinary protozoan parasite Trichomonas vaginalis (TV) is one of the leading risk factors of genital HIV shedding, sexual and perinatal HIV transmission. The majority of TV clinical isolates carry endosymbiont dsRNA viruses (TVV). We have recently shown that TVV causes a profound TLR-3-dependent inflammatory reaction by human cervical and vaginal epithelial cells; however, the effects of TVV on HIV host cells and HIV replication have not been investigated to date. We hypothesized that the immunoinflammatory responses to TVV are at least partially responsible for trichomoniasis-attributable HIV risk. Methods: Peripheral blood mononuclear cells were stimulated with clinical TV isolates and purified TVV, followed by infection with primary isolates of CXCR4-and CCR5-tropic HIV-1. Supernatants were collected at multiple time points over a period of 15 days to measure HIV-1 p24 by ELISA and immune mediators by multiplex immunoassays. ANOVA was applied, and P < 0.05 was considered significant. Results: TVV-positive TV induced significantly higher proinflammatory responses as compared to TVV negative TV isolates. TVV-positive TV up-regulated proinflammatory and Th1/ Th2 cytokines and enhanced those responses when applied together with other immune stimulants e.g. IL-2 and PHA. While levels of proinflammatory responses (IL-1-beta, TNF-alpha and IL-8) showed a tendency to subside after 72h, the levels of immunoregulatory cytokines e.g. IFN-gamma, IL-4, IL-5, IL-13 and IL-12p70 continued to rise. Purified TVV virions induced comparable immune activation. TVV + TV pre-exposure caused a 50-fold increase in p24 levels and the enhancement lasted for at least 15 days (p < 0.001). Conclusions: Our data support the hypothesis that TVV virus causes inflammation and immune cell activation capable of enhancing and propagating HIV replication and thus should be further investigated as a plausible target for HIV prophylaxis. (NIAID HU CFAR 5P30AI0600354-08, R56AI091889 and R01AI079085).
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