CATIONIC POLYPEPTIDES ARE REQUIRED FOR ANTI-HIV-1-ACTIVITY OF HUMAN VAGINAL FLUID.

This study by researchers at the University of Central Florida Biomolecular Science Center demonstrated that MatTek’s EpiVaginal human cervico-vaginal tissue equivalent is an excellent in vitro model for investigating HIV-1 infection via the mucosal surfaces of the vagina, as well as agents that may inhibit/prevent this route of HIV-1 infection, because of the tissue’s ability to become infected when exposed to HIV-1 virus. Mucosal surfaces of the vagina are the portals for heterosexual transmission of HIV-1 and therefore play a fundamental role in the pathogenesis of primary infection. In the search for direct biological evidence for the role of human vaginal fluid in innate host defense, researchers in the Department of Molecular Biology and Microbiology at the University of Central Florida Biomolecular Science Center characterized the anti-HIV-1 function of cationic polypeptides within minimally manipulated vaginal fluid. In the current study researchers revealed that vaginal fluid confers intrinsic anti-HIV-1 properties against both X4 and R5 strains of HIV-1 and could protect against HIV-1 infection and reduce proviral genome integration in (EpiVaginal) organotypic cultures of human cervicovaginal tissue. The majority of this activity was contained in the cationic polypeptide fraction, and the depletion of cationic polypeptides using a selective cation exchange resin ablated most of the intrinsic activity against HIV-1. By adding the cationic polypeptide fraction to depleted vaginal fluid, researchers were able to restore activity against HIV-1. Using a proteomic approach, they identified 18 cationic polypeptides within vaginal fluid, nearly all of which are either known antimicrobials or have other purported roles in host defense. Interestingly, physiologic concentrations of 13 of the cationic polypeptides were not active alone against HIV-1, yet in concert they partially restored the anti-HIV-1 activity of cation-depleted vaginal fluid. These results suggest that synergism between cationic polypeptides is complex, and full anti-HIV-1 activity probably involves the aggregate of the cationic peptides and proteins in vaginal fluid.

Anti-HIV-1, Anti-HIV-1 function, Anti-microbial, Anti-microbials, Antimicrobial, Antimicrobials, Cationic polypeptides, Cervical glands, Dendritic cells, EpiVaginal, HIV-1, Heterosexual transmission, Host defense, Human beta-defensins (HBDs), Human cervicovaginal tissue, Human neutrophil peptides (HNP-1, 2, 3), Human vaginal fluid, Innate host defense, Intrinsic anti-HIV-1 properties, Lactoferrin, Lysozyme, Mucosal surfaces, Neutrophils, Organotypic vaginal-ectocervical tissue, Proviral genome integration, R5 strain, Secretory leukocyte protease inhibitor (SLPI), Vaginal epithelial cells, X4 strain

Cationic Polypeptides, HIV-1