Abstract
BackgroundHIV-1 is usually transmitted in the presence of semen. We have shown that semen boosts HIV-1 infection and contains fragments of prostatic acid phosphatase (PAP) forming amyloid aggregates termed SEVI (semen-derived enhancer of viral infection) that promote virion attachment to target cells. Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial.ResultsHere, we established methods allowing the meaningful analysis of semen by minimizing its cytotoxic effects and partly recapitulating the conditions encountered during sexual HIV-1 transmission. We show that semen rapidly and effectively enhances the infectivity of HIV-1, HIV-2, and SIV. This enhancement occurs independently of the viral genotype and coreceptor tropism as well as the virus producer and target cell type. Semen-mediated enhancement of HIV-1 infection was also observed under acidic pH conditions and in the presence of vaginal fluid. We further show that the potency of semen in boosting HIV-1 infection is donor dependent and correlates with the levels of SEVI.ConclusionsOur results show that semen strongly enhances the infectivity of HIV-1 and other primate lentiviruses and that SEVI contributes to this effect. Thus, SEVI may play an important role in the sexual transmission of HIV-1 and addition of SEVI inhibitors to microbicides may improve their efficacy.
Highlights
HIV-1 is usually transmitted in the presence of semen
We have previously shown that fragments of the abundant semen protein prostatic acidic phosphatase (PAP) form amyloid structures that capture HIV-1 virions and promote their attachment to target cells [17]
We reduced the final concentrations of SE in cell culture by pre-incubating SE with the HIV-1 virions and adding small volumes of these HIV/SE mixtures and serial dilutions thereof, to comparatively large TZM-bl cell cultures (Figure 1A)
Summary
HIV-1 is usually transmitted in the presence of semen. Despite its importance for the global spread of HIV-1, the effect of semen on virus infection is controversial. HIV-1 has infected more than 60 million people and caused about 25 million deaths [2]. In 2008 alone, there were 2.7 million new HIV-1 infections and 2.0 million AIDS-related fatalities. The great majority of all HIV-1 transmissions results from unprotected sexual intercourse. Despite the rapid spread of HIV-1, the estimated rate of transmission per sexual intercourse is surprisingly low: male to female virus transmission occurs about once in every 1,00010,000 unprotected vaginal act [3,4].
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