Retrocyclin RC-101 Blocks HIV-1 Transmission Across Cervical Mucosa in an Organ Culture
Abbreviated Journal Title
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
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.
Jaids-Journal of Acquired Immune Deficiency Syndromes
"Retrocyclin RC-101 Blocks HIV-1 Transmission Across Cervical Mucosa in an Organ Culture" (2012). Faculty Bibliography 2010s. 2531.