title: Retrocyclin RC-101 blocks HIV-1 transmission across cervical mucosa in an organ culture.
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.
authors.affiliation: Department of Infectious Diseases and Microbiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. pgupta1@pitt.edu
authors.forename: Phalguni
authors.initials: P
authors.lastname: Gupta
authors.forename: Deena
authors.initials: D
authors.lastname: Ratner
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Bruce
authors.initials: B
authors.lastname: Patterson
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Rohan
authors.forename: Todd A
authors.initials: TA
authors.lastname: Reinhart
authors.forename: Velpandi
authors.initials: V
authors.lastname: Ayyavoo
authors.forename: Xioli
authors.initials: X
authors.lastname: Huang
authors.forename: Dorothy L
authors.initials: DL
authors.lastname: Patton
authors.forename: Bharat
authors.initials: B
authors.lastname: Ramratnam
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Cole
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000633:toxicity; D002584:Cervix Uteri / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009092:Mucous Membrane / Q000821:virology*; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000890:Anti-Infective Agents; D016207:Cytokines; D010455:Peptides; C450143:RC 101