Prostatic acid phosphatase-derived peptides do not enhance HIV-1 infection
J.A. Martellini1, A.L. Cole1, P. Svoboda2, L.-M. Chen1, K.X. Chai1, B. Gangrade3, O.E. Sorensen4, J. Pohl2, A.M. Cole1
1University of Central Florida College of Medicine, Molecular Biology and Microbiology, Orlando, United States, 2Centers for Disease Control and Prevention, Atlanta, United States, 3Center for Reproductive Medicine, Orlando, United States, 4Lund University, Lund, Sweden
Background: HIV-1 sexual transmission is likely inhibited by the innate antimicrobial components of the mucosal surfaces and secretions of the reproductive tract. Recently, we reported that whole human seminal plasma (SP) prevented HIV-1 infection in vitro even when diluted 3200-fold, which was due to the high concentration and number of cationic polypeptides in the fluid. Other groups have recently reported that naturally occurring peptidic fragments from the SP-derived protein prostatic acid phosphatase (PAP) are capable of forming amyloid fibrils, which enhanced HIV-1 infection in vitro.
Methods: In order to understand the biological relevance of this putative proviral effect, we extended their studies in the presence of whole human SP. Two predominant PAP-derived peptides were agitated at 1400 rpm for 18hrs at 37ºC and incubated at physiological and supraphysiological concentrations with or without SP.
Results: While PAP peptides and their amyloid fibrils were proviral in the absence of SP, the presence of SP diluted as much as 400-fold completely ablated PAP peptide-mediated proviral activity. Tricine/SDS-PAGE revealed that PAP peptides and amyloid fibrils incubated with SP were partially degraded within 1 hr of incubation, and by 4 hrs were completely degraded. There are multiple known proteases in SP, but the chymotrypsin-like prostate specific antigen (PSA) is commonly referenced as the primary protease responsible for SP degradation at neutral pH. Incubation of PAP peptides with PSA revealed that physiological and sub-physiological concentrations of PSA completely degraded PAP peptides and their amyloid fibrils into proteolytic fragments that lost their HIV-1-enhancing activity.
Conclusions: While human SP is a complex biological fluid, containing both antiviral and proviral factors, our results suggest that the proviral activities exhibited by PAP peptides and their corresponding amyloid fibrils in vitro are unlikely translated to the physiological condition in vivo in human SP.
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