title: 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.
authors.affiliation: Department of Molecular Biology & Microbiology, Biomolecular Science Center, Burnett School of Biomedical Sciences at the University of Central Florida College of Medicine, Orlando, Florida, United States of America.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Martellini
authors.forename: Amy L
authors.initials: AL
authors.lastname: Cole
authors.forename: Pavel
authors.initials: P
authors.lastname: Svoboda
authors.forename: Olga
authors.initials: O
authors.lastname: Stuchlik
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Chen
authors.forename: Karl X
authors.initials: KX
authors.lastname: Chai
authors.forename: Bhushan K
authors.initials: BK
authors.lastname: Gangrade
authors.forename: Ole E
authors.initials: OE
authors.lastname: Sørensen
authors.forename: Jan
authors.initials: J
authors.lastname: Pohl
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Cole
mesh_terms: D000135:Acid Phosphatase; D000682:Amyloid; D004305:Dose-Response Relationship, Drug; D016322:HIV Enhancer; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000494:pharmacology*; D012661:Semen / Q000821:virology*; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D000682:Amyloid; D010446:Peptide Fragments; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases; D012697:Serine Endopeptidases; C485595:matriptase; D017430:Prostate-Specific Antigen