HIV-1 Enhancing Effect of Prostatic Acid Phosphatase Peptides Is Reduced in Human Seminal Plasma

Abstract

We recently reported that HIV-1 infection can be inhibited by innate antimicrobial components of human seminal plasma (SP). Conversely, naturally occurring peptidic fragments from the SP-derived prostatic acid phosphatase (PAP) have been reported to form amyloid fibrils called “SEVI” and enhance HIV-1 infection in vitro. In order to understand the biological consequence of this proviral effect, we extended these studies in the presence of human SP. PAP-derived peptides were agitated to form SEVI and incubated in the presence or absence of SP. While PAP-derived peptides and SEVI alone were proviral, the presence of 1% SP ablated their proviral activity in several different anti-HIV-1 assays. The anti-HIV-1 activity of SP was concentration dependent and was reduced following filtration. Supraphysiological concentrations of PAP peptides and SEVI incubated with diluted SP were degraded within hours, with SP exhibiting proteolytic activity at dilutions as high as 1∶200. Sub-physiological concentrations of two prominent proteases of SP, prostate-specific antigen (PSA) and matriptase, could degrade physiological and supraphysiological concentrations of PAP peptides and SEVI. While human SP is a complex biological fluid, containing both antiviral and proviral factors, our results suggest that PAP peptides and SEVI may be subject to naturally occurring proteolytic components capable of reducing their proviral activity.

No SEVI-mediated enhancement of rectal HIV-1 transmission of HIV-1 in two humanized mouse cohorts

“…Furthermore, physiological concentrations of zinc and copper have been shown to inhibit fibrilization of SEVI in vitro (Sheftic et al, 2012). While not directly applicable to our experiments, one study found the enhancing activity of SEVI to be neutralized in the presence of human seminal fluid through the action of enzymes that degrade SEVI into non-enhancing fragments (Martellini et al, 2011). Another factor that might affect SEVI-mediated enhancement of HIV transmission is whether transmission occurs predominantly through free virus or cell-associated virus, a subject not clearly understood at this time.…”

Mycoplasma genitalium promotes epithelial crossing and peripheral blood mononuclear cell infection by HIV-1

“…This is a complex microenvironment composed of sperm and seminal lymphocytes (both of which can bind and carry HIV 22–24 ), seminal fluid components, 25,26 and non-HIV sexually transmitted disease pathogens (in the semen donor or the female genital–mucosal tissues 1,27–30 ). All of these affect HIV passage across the epithelium and then influence its infectivity and replication in its target cells beneath the epithelium.…”

Exosomes in semen: opportunities as a new tool in prostate cancer diagnosis

“…SE have a role in immunesuppression (17) and affects the complement system (18). It was reported that exposure of the female reproductive tract to semen results in immune-modulatory events which influence the outcome of HIV-1 replication within the genital mucosa (19,20). HIV-1 and human papilloma virus (HPV) is transmitted primarily through sexual contact and semen is the primary vector (21).…”

“…The correlation between SE, immunity and HIV-1 transmission have been demonstrated (22). SE may either enhance or block replication of sexually transmitted pathogens, such as HIV-1 (19,20). Madison et al showed that semen exosomes purified from healthy human donors alter HIV-1 replication, through alteration in intravirion reverse transcriptase (RT) activity and protein composition, drastically decreasing HIV infectivity (23).…”