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Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI.

Kim KA, Yolamanova M, Zirafi O, Roan NR, Staendker L, Forssmann WG, Burgener A, Dejucq-Rainsford N, Hahn BH, Shaw GM, Greene WC, Kirchhoff F, Münch J - Retrovirology (2010)

Bottom Line: Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial.We show that semen rapidly and effectively enhances the infectivity of HIV-1, HIV-2, and SIV.Our results show that semen strongly enhances the infectivity of HIV-1 and other primate lentiviruses and that SEVI contributes to this effect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Molecular Virology, University Hospital Ulm, 89081 Ulm, Germany.

ABSTRACT

Background: HIV-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.

Results: Here, 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.

Conclusions: Our 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.

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Semen inhibits trans-infection of T cells by DC-SIGN. B-THP-1-DC-SIGN cells were treated with the indicated concentration of SE, SE-F or SE-P for 30 min, subsequently exposed to R5 HIV-1 for 30 min, washed and cocultivated with CEM-M7 cells. The levels of infection mediated by B-THP-1 cells, which do not express DC-SIGN, and the absence of cells (medium) are also shown as controls. Shown are average values ± SD derived from triplicate infections. Stars indicate cytotoxicity, infection rates obtained after infection with 2% and 10% SE, SE-F or SE-P treated virus were close to background luciferase activities of uninfected cells.
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Figure 5: Semen inhibits trans-infection of T cells by DC-SIGN. B-THP-1-DC-SIGN cells were treated with the indicated concentration of SE, SE-F or SE-P for 30 min, subsequently exposed to R5 HIV-1 for 30 min, washed and cocultivated with CEM-M7 cells. The levels of infection mediated by B-THP-1 cells, which do not express DC-SIGN, and the absence of cells (medium) are also shown as controls. Shown are average values ± SD derived from triplicate infections. Stars indicate cytotoxicity, infection rates obtained after infection with 2% and 10% SE, SE-F or SE-P treated virus were close to background luciferase activities of uninfected cells.

Mentions: Our result that SE enhances HIV-1 infection seems to be contradictory to previous studies reporting that seminal plasma (SE-P) impairs the capture and transmission of HIV-1 by DC-SIGN [14] and inhibits virus infection [15]. To determine the effect of SE and SE-P on HIV-1 transmission by DC-SIGN we used B-THP-1-DC-SIGN and CEM-M7 cells. As expected [14], expression of DC-SIGN strongly enhanced transmission of HIV-1 to CEM-M7 indicator cells (Figure 5). In agreement with previous results [14], pre-treatment of cells with SE, SE-F and SE-P potently inhibited DC-SIGN-mediated transmission of HIV-1 (Figure 5). In contrast, SEVI amplified infection of T cells by HIV-1 particles bound to DC-SIGN-expressing dendritic or B-THP-1 cells even further [[17], data not shown]. Thus, SEVI generally facilitates HIV-1 infection, whereas SE also contains a specific inhibitor that overcomes the enhancing effect of SEVI in the case of DC-SIGN-mediated virus transmission.


Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI.

Kim KA, Yolamanova M, Zirafi O, Roan NR, Staendker L, Forssmann WG, Burgener A, Dejucq-Rainsford N, Hahn BH, Shaw GM, Greene WC, Kirchhoff F, Münch J - Retrovirology (2010)

Semen inhibits trans-infection of T cells by DC-SIGN. B-THP-1-DC-SIGN cells were treated with the indicated concentration of SE, SE-F or SE-P for 30 min, subsequently exposed to R5 HIV-1 for 30 min, washed and cocultivated with CEM-M7 cells. The levels of infection mediated by B-THP-1 cells, which do not express DC-SIGN, and the absence of cells (medium) are also shown as controls. Shown are average values ± SD derived from triplicate infections. Stars indicate cytotoxicity, infection rates obtained after infection with 2% and 10% SE, SE-F or SE-P treated virus were close to background luciferase activities of uninfected cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2914040&req=5

Figure 5: Semen inhibits trans-infection of T cells by DC-SIGN. B-THP-1-DC-SIGN cells were treated with the indicated concentration of SE, SE-F or SE-P for 30 min, subsequently exposed to R5 HIV-1 for 30 min, washed and cocultivated with CEM-M7 cells. The levels of infection mediated by B-THP-1 cells, which do not express DC-SIGN, and the absence of cells (medium) are also shown as controls. Shown are average values ± SD derived from triplicate infections. Stars indicate cytotoxicity, infection rates obtained after infection with 2% and 10% SE, SE-F or SE-P treated virus were close to background luciferase activities of uninfected cells.
Mentions: Our result that SE enhances HIV-1 infection seems to be contradictory to previous studies reporting that seminal plasma (SE-P) impairs the capture and transmission of HIV-1 by DC-SIGN [14] and inhibits virus infection [15]. To determine the effect of SE and SE-P on HIV-1 transmission by DC-SIGN we used B-THP-1-DC-SIGN and CEM-M7 cells. As expected [14], expression of DC-SIGN strongly enhanced transmission of HIV-1 to CEM-M7 indicator cells (Figure 5). In agreement with previous results [14], pre-treatment of cells with SE, SE-F and SE-P potently inhibited DC-SIGN-mediated transmission of HIV-1 (Figure 5). In contrast, SEVI amplified infection of T cells by HIV-1 particles bound to DC-SIGN-expressing dendritic or B-THP-1 cells even further [[17], data not shown]. Thus, SEVI generally facilitates HIV-1 infection, whereas SE also contains a specific inhibitor that overcomes the enhancing effect of SEVI in the case of DC-SIGN-mediated virus transmission.

Bottom Line: Despite its importance for the global spread of HIV-1, however, the effect of semen on virus infection is controversial.We show that semen rapidly and effectively enhances the infectivity of HIV-1, HIV-2, and SIV.Our results show that semen strongly enhances the infectivity of HIV-1 and other primate lentiviruses and that SEVI contributes to this effect.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Molecular Virology, University Hospital Ulm, 89081 Ulm, Germany.

ABSTRACT

Background: HIV-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.

Results: Here, 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.

Conclusions: Our 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.

Show MeSH
Related in: MedlinePlus