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THE RETROCYCLIN ANALOGUE RC-101 PREVENTS HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 INFECTION OF A MODEL HUMAN CERVICOVAGINAL TISSUE CONSTRUCT.
Cole1, A.L., Herasimtschuk1, A., Gupta2, P., Waring3, A., Lehrer3, R., and Cole1, A.M.
1Department of Molecular Biology & Microbiology,
Biomolecular Science Center, Burnett
College of Biomedical Sciences at University of Central Florida, Orlando, FL, 2Department of Infectious Diseases and Microbiology, University of Pittsburgh, PA, and 3Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
Immunology, (online edition), 23-Jan-2007.
Keywords: θ-defensin, AIDS, Acquired immunodeficieny syndrome, Anti-microbial, Anti-microbial peptide, Antimicrobial, Antimicrobial peptide, Cervicovaginal tissue , Defensin, EpiVaginal, HIV, HIV-1, Human cervicovaginal tissue , Human immunodeficiency virus, Inflammation, Inflammatory, Inflammatory cytokines, Microbicide, RC-101, Retrocyclin, Retrocyclins, Vagina
Endpoints: HIV-1 copy number, LDH inflammatory reactions, MTT viability
Materials Tested: EpiVaginal, HIV-1 BaL, MTT, PM1, RC-101, TZM-bl
Summary:
Retrocyclins are cyclic antimicrobial peptides that exhibit potent activity towards a broad range of primary and laboratory-adapted strains of human immunodeficiency virus type 1 (HIV-1) in vitro.
This study by researchers at the University of Central Florida, University of Pittsburgh, PA, and the David Geffen School of Medicine at UCLA shows that RC-101, an analogue of retrocyclin, prevented HIV-1 infection in EpiVaginal, an organ-like construct of human cervicovaginal tissue, and retained full activity in the presence of vaginal fluid.
The peptide remained within the cervicovaginal tissues throughout the 9-day incubation period without altering tissue viability, inducing damage or inducing the release of inflammatory cytokines.
Collectively, these data support the potential development of RC-101 as a topical microbicide to prevent HIV-1 infection and transmission.
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