Cationic polypeptides contribute to the anti‐HIV‐1 activity of human seminal plasma

Abstract

Mucosal surfaces of the reproductive tract as well as their secretions have important roles in preventing sexual transmission of HIV-1. In the current study, the majority of the intrinsic anti-HIV-1 activity of human seminal plasma (SP) was determined to reside in the cationic polypeptide fraction. Antiviral assays utilizing luciferase reporter cells and lymphocytic cells revealed the ability of whole SP to prevent HIV-1 infection, even when SP was diluted 3200-fold. Subsequent fractionation by continuous flow acid-urea (AU)-PAGE and antiviral testing revealed that cationic polypeptides within SP were responsible for the majority of anti-HIV-1 activity. A proteomic approach was utilized to resolve and identify 52 individual cationic polypeptides that contribute to the aggregate anti-HIV-1 activity of SP. One peptide fragment of semenogelin I, termed SG-1, was purified from SP by a multistep chromatographic approach, protein sequenced, and determined to exhibit anti-HIV-1 activity against HIV-1. Anti-HIV-1 activity was transient, as whole SP incubated for prolonged time intervals exhibited a proportional decrease in anti-HIV-1 activity that was directly attributed to the degradation of semenogelin I peptides. Collectively, these results indicate that the cationic polypeptide fraction of SP is active against HIV-1, and that semenogelin-derived peptides contribute to the intrinsic anti-HIV-1 activity of SP.

Role of Semen in Modulating the Female Genital Tract Microenvironment – Implications for HIV Transmission

“…Seminal fluid and whole semen have demonstrated anti-HIV activity in vitro in T-lymphocyte cell lines. 54 Cationic polypeptides contained in seminal plasma 55 and reactive oxygen species produced by seminal leukocytes and spermatozoa 56 provide intrinsic antiviral activity against HIV-1. Seminal plasma also blocks the attachment of HIV-1 to DC-SIGN, thus preventing viral transfer to CD4 + target cells in vitro.…”

Influence of Common Mucosal Co‐Factors on HIV Infection in the Female Genital Tract

“…In contrast, other cationic polypeptides such as semenogelin contribute to anti-HIV activity in SP. 127 Furthermore, deposition of semen into the acidic vaginal environment can raise the pH, which may decrease 116,128 or increase 129 the infectivity of the virus.…”

Characterization of the Influence of Semen-Derived Enhancer of Virus Infection on the Interaction of HIV-1 with Female Reproductive Tract Tissues

“…Some investigations suggest a proinflammatory role when semen is introduced to the genital tract such that it alters the activation state of potential target cells and neutralizes the native acidic pH (5). Still, findings presented elsewhere suggest a target cell-specific protective effect of semen (6)(7)(8)(9). Male-to-female HIV-1 transmission events are a consequence of exposure to semen harboring infectious virus (10).…”