Limits...
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.

Show MeSH

Related in: MedlinePlus

The HIV enhancing activity of individual SE samples correlates with SEVI concentrations. (A) Enhancement of HIV-1 infection by SE samples from 14 different donors. R5 HIV-1 stocks were mixed with 10% (v/v) of the SE samples or PBS and used for infection of TZM-bl indicator cells. Similar results were obtained using SE samples from more than 80 additional donors. Reactivity of anti-SEVI-antiserum from guinea pigs to (B) the indicated monomeric peptides or IVES, a peptide containing the reverse amino acid sequence of PAP248-286 and full-length PAP. (C) SEVI fibrils or (D) pooled SE spiked with SEVI. Similar results were obtained using an antiserum from rabbits. (E) Correlation between the magnitude of enhancement of HIV-1 infection by individual SE samples and the quantity of SEVI/PAP248-286 detectable using the anti-SEVI antiserum.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2914040&req=5

Figure 7: The HIV enhancing activity of individual SE samples correlates with SEVI concentrations. (A) Enhancement of HIV-1 infection by SE samples from 14 different donors. R5 HIV-1 stocks were mixed with 10% (v/v) of the SE samples or PBS and used for infection of TZM-bl indicator cells. Similar results were obtained using SE samples from more than 80 additional donors. Reactivity of anti-SEVI-antiserum from guinea pigs to (B) the indicated monomeric peptides or IVES, a peptide containing the reverse amino acid sequence of PAP248-286 and full-length PAP. (C) SEVI fibrils or (D) pooled SE spiked with SEVI. Similar results were obtained using an antiserum from rabbits. (E) Correlation between the magnitude of enhancement of HIV-1 infection by individual SE samples and the quantity of SEVI/PAP248-286 detectable using the anti-SEVI antiserum.

Mentions: All experiments described above were performed with pooled semen obtained from more than 20 individual donors. To assess whether the enhancing activity may be donor-dependent, we collected and analyzed SE samples from 14 different individuals. All SE samples were allowed to liquefy for 30 min and subsequently kept frozen until further use. Notably, they were processed and tested together for their ability to promote HIV-1 infection. We found that all SE samples enhanced HIV-1 infection, albeit with strikingly different efficiencies ranging from 2- to about 50-fold (Figure 7A). Thus, in addition to the viral load and other factors, the potency of SE in enhancing the infectiousness of HIV-1 particles may also affect the rates of virus transmission. Notably, fresh liquefied ejaculates enhanced HIV-1 infection about as effectively as SE samples that had undergone a freeze/thaw cycle (data not shown). Thus, the presence of living spermatozoa capturing virions by heparan sulfate [16] or other cells did not interfere with SE-mediated enhancement of HIV infection.


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)

The HIV enhancing activity of individual SE samples correlates with SEVI concentrations. (A) Enhancement of HIV-1 infection by SE samples from 14 different donors. R5 HIV-1 stocks were mixed with 10% (v/v) of the SE samples or PBS and used for infection of TZM-bl indicator cells. Similar results were obtained using SE samples from more than 80 additional donors. Reactivity of anti-SEVI-antiserum from guinea pigs to (B) the indicated monomeric peptides or IVES, a peptide containing the reverse amino acid sequence of PAP248-286 and full-length PAP. (C) SEVI fibrils or (D) pooled SE spiked with SEVI. Similar results were obtained using an antiserum from rabbits. (E) Correlation between the magnitude of enhancement of HIV-1 infection by individual SE samples and the quantity of SEVI/PAP248-286 detectable using the anti-SEVI antiserum.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: The HIV enhancing activity of individual SE samples correlates with SEVI concentrations. (A) Enhancement of HIV-1 infection by SE samples from 14 different donors. R5 HIV-1 stocks were mixed with 10% (v/v) of the SE samples or PBS and used for infection of TZM-bl indicator cells. Similar results were obtained using SE samples from more than 80 additional donors. Reactivity of anti-SEVI-antiserum from guinea pigs to (B) the indicated monomeric peptides or IVES, a peptide containing the reverse amino acid sequence of PAP248-286 and full-length PAP. (C) SEVI fibrils or (D) pooled SE spiked with SEVI. Similar results were obtained using an antiserum from rabbits. (E) Correlation between the magnitude of enhancement of HIV-1 infection by individual SE samples and the quantity of SEVI/PAP248-286 detectable using the anti-SEVI antiserum.
Mentions: All experiments described above were performed with pooled semen obtained from more than 20 individual donors. To assess whether the enhancing activity may be donor-dependent, we collected and analyzed SE samples from 14 different individuals. All SE samples were allowed to liquefy for 30 min and subsequently kept frozen until further use. Notably, they were processed and tested together for their ability to promote HIV-1 infection. We found that all SE samples enhanced HIV-1 infection, albeit with strikingly different efficiencies ranging from 2- to about 50-fold (Figure 7A). Thus, in addition to the viral load and other factors, the potency of SE in enhancing the infectiousness of HIV-1 particles may also affect the rates of virus transmission. Notably, fresh liquefied ejaculates enhanced HIV-1 infection about as effectively as SE samples that had undergone a freeze/thaw cycle (data not shown). Thus, the presence of living spermatozoa capturing virions by heparan sulfate [16] or other cells did not interfere with SE-mediated enhancement of HIV infection.

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