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

    Authors

    P. Gupta; D. Ratner; M. Ding; B. Patterson; L. C. Rohan; T. A. Reinhart; V. Ayyavoo; X. L. Huang; D. L. Patton; B. Ramratnam;A. M. Cole

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    Abbreviated Journal Title

    Jaids

    Keywords

    retrocyclin; HIV; organ culture; microbicide; IMMUNODEFICIENCY-VIRUS-INFECTION; FEMALE GENITAL-TRACT; IN-VITRO; TOPICAL MICROBICIDES; CANDIDATE MICROBICIDES; REVERSE-TRANSCRIPTASE; VAGINAL MICROBICIDE; EXPLANT CULTURE; NONOXYNOL-9 USE; T-CELLS; Immunology; Infectious Diseases

    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.

    Journal Title

    Jaids-Journal of Acquired Immune Deficiency Syndromes

    Volume

    60

    Issue/Number

    5

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    455

    Last Page

    461

    WOS Identifier

    WOS:000306994500004

    ISSN

    1525-4135

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