期刊
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
卷 60, 期 5, 页码 455-461出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e318258b420
关键词
retrocyclin; HIV; organ culture; microbicide
资金
- National Institute of Health [R01 HD052436, NIH U19 AI65430]
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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