Assessment of the range of the HIV-1 infectivity enhancing effect of individual human semen specimen and the range of inhibition by EGCG

HIV-infection is an imminent health issue, with an estimated 33 million individuals infected worldwide according to UNAIDS [1]. Globally, most HIV infections occur by heterosexual transmission (for review see [2]). Sexual HIV-1-transmission depends on viral and multiple host factors that altogether have not been entirely unraveled [3], and a direct role of semen has been described by several groups (reviewed in [4]).Recently, it has been reported that human ejaculate acts as a potent enhancer of HIV infectivity [5]. This enhancement of infectivity is mediated by a factor, termed Semen-derived Enhancer of Virus Infection (SEVI) [5]. SEVI was identified to be a peptide fragment of the semen marker prostatic acidic phosphatase (PAP) that, upon proteolytic release, forms amyloid fibrils. These fibrils capture HIV virions and direct them to target cells, where they facilitate the fusion of virus and host cell [6].Interestingly, it has been previously demonstrated that epigallocatechin-3-gallate (EGCG), the major active constituent of green tea, can inhibit the infectivity enhancing effect of SEVI, possibly by interference with de novo SEVI formation or by degradation of present preformed PAP-derived amyloid fibrils [7]. This observation may be important for possible application of EGCG in microbicidal vaginal and rectal gels that could reduce HIV transmission rates [8,9].To date, published studies on SEVI (and EGCG) are predominantly based on in vitro experiments carried out either with pooled human semen or with fibrils formed from synthetic PAP-fragment peptides (PAP248-286) [5,7]. Hence, the aim of the current study was to determine the range and variability of the HIV-1 infectivity enhancing properties and the effect of EGCG on infectivity enhancement within a cohort of individual human semen samples, and to describe the clinical semen characteristics that are potentially associated with the augmentation of HIV-1-infectivity. In addition, this is the first study that