title: Inhibition of HIV-1 infection in ex vivo cervical tissue model of human vagina by palmitic acid; implications for a microbicide development.
abstract: BACKGROUND
  Approximately 80% of all new HIV-1 infections are acquired through sexual contact. Currently, there is no clinically approved microbicide, indicating a clear and urgent therapeutic need. We recently reported that palmitic acid (PA) is a novel and specific inhibitor of HIV-1 fusion and entry. Mechanistically, PA inhibits HIV-1 infection by binding to a novel pocket on the CD4 receptor and blocks efficient gp120-to-CD4 attachment. Here, we wanted to assess the ability of PA to inhibit HIV-1 infection in cervical tissue ex vivo model of human vagina, and determine its effect on Lactobacillus (L) species of probiotic vaginal flora.
  
  
  RESULTS
  Our results show that treatment with 100-200 µM PA inhibited HIV-1 infection in cervical tissue by up to 50%, and this treatment was not toxic to the tissue or to L. crispatus and jensenii species of vaginal flora. In vitro, in a cell free system that is independent of in vivo cell associated CD4 receptor; we determined inhibition constant (Ki) to be ∼2.53 µM.
  
  
  CONCLUSIONS
  These results demonstrate utility of PA as a model molecule for further preclinical development of a safe and potent HIV-1 entry microbicide inhibitor.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, United States of America.
authors.forename: Xudong
authors.initials: X
authors.lastname: Lin
authors.forename: Elena E
authors.initials: EE
authors.lastname: Paskaleva
authors.forename: William
authors.initials: W
authors.lastname: Chang
authors.forename: Alexander
authors.initials: A
authors.lastname: Shekhtman
authors.forename: Mario
authors.initials: M
authors.lastname: Canki
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism; D002584:Cervix Uteri / Q000187:drug effects / Q000821:virology*; D055808:Drug Discovery; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007778:Lactobacillus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D019308:Palmitic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D014621:Vagina / Q000187:drug effects / Q000821:virology*
chemical_list: D000890:Anti-Infective Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019308:Palmitic Acid