title: Antiviral activity of retrocyclin RC-101, a candidate microbicide against cell-associated HIV-1.
abstract: Microbicides have been evaluated mostly against cell-free HIV-1. Because semen contains both cell-free and cell-associated HIV-1, HIV-1 transmission could occur via either or both sources. Therefore, it is important to examine the antiviral activity of microbicides against cell-associated HIV-1. The cyclic antimicrobial peptide retrocyclin RC-101 has been shown previously to have antiviral activity against cell-free HIV-1, with no associated cellular toxicity. In this article we have examined the antiviral activity of RC-101 against cell-associated HIV-1. The results demonstrate potent antiviral activity of RC-101 against cell-cell HIV-1 transmission in both CD4-dependent and CD4-independent assays against CCR5- and CXCR4-tropic HIV-1, with no cellular toxicity. Furthermore, this antiviral activity was retained in the presence of human seminal plasma. The potent antiviral activity of RC-101 against cell-associated HIV-1 reported here, and the previously reported antiviral activity in cervical tissues, suggest that RC-101 is an excellent and promising microbicide candidate against HIV-1.
authors.affiliation: Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh , Pittsburgh, Pennsylvania 15261, USA. pgupta1@pitt.edu
authors.forename: Phalguni
authors.initials: P
authors.lastname: Gupta
authors.forename: Carol
authors.initials: C
authors.lastname: Lackman-Smith
authors.forename: Beth
authors.initials: B
authors.lastname: Snyder
authors.forename: Deena
authors.initials: D
authors.lastname: Ratner
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Rohan
authors.forename: Dorothy
authors.initials: D
authors.lastname: Patton
authors.forename: Bharat
authors.initials: B
authors.lastname: Ramratnam
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Cole
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D023082:Defensins / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D023082:Defensins; D010455:Peptides; C450143:RC 101; C450142:theta-defensin