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

Institute of Molecular Virology, University Hospital Ulm, 89081 Ulm, Germany.
Retrovirology (Impact Factor: 4.19). 06/2010; 7(1):55. DOI: 10.1186/1742-4690-7-55
Source: PubMed


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.
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.
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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    • "TKO-BLT mice develop high levels of human immune system reconstitution, are susceptible to HIV-1 infection via intrarectal inoculation and exhibit hallmarks of human HIV infection such as CD4 þ T cell depletion and general immune activation (Lavender et al., 2013). The most dramatic enhancing effects of SEVI and semen in vitro have been observed with low doses of HIV-1 irrespective of the virus strain and producer or target cell type (Kim et al., 2010; Munch et al., 2007). Thus for the in vivo experiments we tested both a high dose of HIV-1 that typically infects approximately half of our mice in the absence of SEVI, and also a lower dose of HIV-1 that generally infects only one out of four or five mice. "
    Article: ID: 41

    No preview · Article · Nov 2015 · Cytokine
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    • "Specifically, proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120), semenogelin 1 (SEM1), and semenogelin 2 (SEM2) form fibrils that boost infectivity by electrostatically facilitating viral attachment to target cells (Arnold et al., 2012; Münch et al., 2007; Roan et al., 2014, 2011; Usmani et al., 2014). This enhancement of infection can be as large as several orders of magnitude and is independent of viral genotype and coreceptor tropism as well as the virus producer and target cell type (Kim et al., 2010). Remarkably, the stimulatory effect of SEVI (semen derived enhancer of viral infection) fibrils is greatest at low virus concentration, similar to the conditions observed in mucosal transmission of HIV, where relatively few virions traverse the mucosal barrier and initiate infection (Roan et al., 2009). "
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    ABSTRACT: Semen harbors amyloid fibrils formed by proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120) and semenogelins (SEM1 and SEM2) that potently enhance HIV infectivity. Amyloid but not soluble forms of these peptides enhance HIV infection. Thus, agents that remodel these amyloid fibrils could prevent HIV transmission. Here, we confirm that the green tea polyphenol, epigallocatechin-3-gallate (EGCG), slowly remodels fibrils formed by PAP248-286 termed SEVI (semen derived enhancer of viral infection) and also exerts a direct anti-viral effect. We elucidate for the first time that EGCG remodels PAP85-120, SEM1(45-107), and SEM2(49-107) fibrils more rapidly than SEVI fibrils. We establish EGCG as the first small molecule that can remodel all four classes of seminal amyloid. The combined anti-amyloid and anti-viral properties of EGCG could have utility in preventing HIV transmission. © 2015. Published by The Company of Biologists Ltd.
    Full-text · Article · Aug 2015 · Biology Open
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    • "We found that SP and SEVI enhanced infection by both HIV-1 and SIVmac, although the effects on the latter were substantially weaker (Figure 1A and B). SP was most effective at 10% (Figure 1A) since 50% begins to cause cytotoxic effects [10,13]. In contrast, the enhancing effect of SEVI did not saturate (Figure 1B). "
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    ABSTRACT: Semen and semen-derived amyloid fibrils boost HIV infection in vitro but their impact on sexual virus transmission in vivo is unknown. Here, we examined the effect of seminal plasma (SP) and semen-derived enhancer of virus infection (SEVI) on vaginal virus transmission in the SIV/rhesus macaque (Macacca mulatta) model. A total of 18 non-synchronized female rhesus macaques (six per group) were exposed intra-vaginally to increasing doses of the pathogenic SIVmac239 molecular clone in the presence or absence of SEVI and SP. Establishment of productive virus infection was assessed by measuring plasma viral RNA loads at weekly intervals. We found that the first infections occurred at lower viral doses in the presence of SP and SEVI compared to the control group. Furthermore, the average peak viral loads during acute infection were about 6-fold higher after exposure to SP- and SEVI-treated virus. Overall infection rates after a total of 27 intra-vaginal exposures to increasing doses of SIV, however, were similar in the absence (4 of 6 animals) and presence of SP (5 of 6), or SEVI (4 of 6). Furthermore, the infectious viral doses required for infection varied considerably and did not differ significantly between these three groups. Semen and SEVI did not have drastic effects on vaginal SIV transmission in the present experimental setting but may facilitate spreading of virus infection after exposure to low viral doses that most closely approximate the in vivo situation.
    Full-text · Article · Dec 2013 · Retrovirology
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