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Retrocyclin RC-101 Blocks HIV-1 Transmission Across Cervical Mucosa in an Organ Culture

Gupta, Phalguni PhD*; Ratner, Deena BS*; Ding, Ming MD*; Patterson, Bruce MD; Rohan, Lisa C. PhD; Reinhart, Todd A. PhD*; Ayyavoo, Velpandi PhD*; Huang, Xioli MD*; Patton, Dorothy L. PhD§; Ramratnam, Bharat MD; Cole, Alexander M. PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 15th, 2012 - Volume 60 - Issue 5 - p 455–461
doi: 10.1097/QAI.0b013e318258b420
Basic and Translational Science

Background: Cervical tissue–based organ cultures have been used successfully to evaluate microbicides for toxicity and antiviral activity. The antimicrobial peptide retrocyclin RC-101 has been shown to have potent anti-HIV activity in cell culture.

Objective: To evaluate RC-101 in organ culture for toxicity and its ability to block HIV-1 transmission across cervical mucosa.

Methods: A cervical tissue–based organ culture was used to measure antiviral activity of RC-101. Cytotoxicity in tissues was determined by immunostaining of cellular proteins and by measuring inflammatory cytokines using real-time reverse transcriptase–polymerase chain reaction and Luminex technology.

Results: RC-101 blocked transmission of both R5 and X4 HIV-1 across cervical mucosa in this organ culture model. Furthermore, film-formulated RC-101 exhibited potent antiviral activity in organ culture. Such antiviral activity of RC-101 was retained in the presence of semen and vaginal fluid. RC-101 showed no cytotoxicity in cervical tissue. Furthermore, RC-101 did not induce proinflammatory cytokine response in tissues. RC-101 also did not have any effect on natural killer cell activity and proliferation of CD4 and CD8 cells and did not show chemotactic activity.

Conclusions: Therefore, because of strong antiviral activity and low cytotoxicity in cervical tissues, RC-101 should be considered as an excellent microbicide candidate against HIV-1.

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*Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA

Department of Pathology, Stanford University, Stanford, CA

Magee Women's Research Institute and the Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA

§Department of Obstetrics and Gynecology, University of Washington, Seattle, WA

Division of Infectious Diseases, Department of Medicine, Brown University, Providence, RI

Department of Molecular Biology and Microbiology, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL.

Correspondence to: Phalguni Gupta, PhD, Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, 426 Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261 (e-mail: pgupta1@pitt.edu).

Supported by the National Institute of Health Grants R01 HD052436 and NIH U19 AI65430.

None of the authors received honoraria from any company or is on the speaker's bureau or CME organizers for any organization.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

Received July 20, 2011

Accepted March 28, 2012

© 2012 Lippincott Williams & Wilkins, Inc.