Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI.
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.
Kim
Kyeong-Ae
KA
Institute of Molecular Virology, University Hospital Ulm, 89081 Ulm, Germany.
Yolamanova
Maral
M
Zirafi
Onofrio
O
Roan
Nadia R
NR
Staendker
Ludger
L
Forssmann
Wolf-Georg
WG
Burgener
Adam
A
Dejucq-Rainsford
Nathalie
N
Hahn
Beatrice H
BH
Shaw
George M
GM
Greene
Warner C
WC
Kirchhoff
Frank
F
Münch
Jan
J
D000135:Acid Phosphatase; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000472:pathogenicity*; D015498:HIV-2 / Q000472:pathogenicity; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011323:Primates; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012661:Semen / Q000821:virology*; D015229:Sexually Transmitted Diseases, Viral; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity; D053585:Virus Attachment
D000682:Amyloid; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases