Title

Retrocyclin Rc-101 Blocks Hiv-1 Transmission Across Cervical Mucosa In An Organ Culture

Keywords

HIV; microbicide; organ culture; retrocyclin

Abstract

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. © 2012 by Lippincott Williams & Wilkins.

Publication Date

8-15-2012

Publication Title

Journal of Acquired Immune Deficiency Syndromes

Volume

60

Issue

5

Number of Pages

455-461

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1097/QAI.0b013e318258b420

Socpus ID

84864279218 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84864279218

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