title: Inhibition of infection and transmission of HIV-1 and lack of significant impact on the vaginal commensal lactobacilli by carbohydrate-binding agents.
abstract: OBJECTIVE
  A selection of carbohydrate-binding agents (CBAs) with different glycan specificities were evaluated for their inhibitory effect against HIV infection and transmission, and their interaction with vaginal commensal bacteria.
  
  
  METHODS
  Several assays were used for the antiviral evaluation: (i) cell-free virus infection of human CD4+ T lymphocyte C8166 cells; (ii) syncytium formation in co-cultures of persistently HIV-1-infected HUT-78/HIV-1 and non-infected CD4+ SupT1 cells; (iii) DC-SIGN-directed capture of HIV-1 particles; and (iv) transmission of DC-SIGN-captured HIV-1 particles to uninfected CD4+ C8166 cells. CBAs were also examined for their interaction with vaginal commensal lactobacilli using several viability, proliferation and adhesion assays.
  
  
  RESULTS
  The CBAs showed efficient inhibitory activity in the nanomolar to low-micromolar range against four events that play a crucial role in HIV-1 infection and transmission: cell-free virus infection, fusion between HIV-1-infected and non-infected cells, HIV-1 capture by DC-SIGN and transmission of DC-SIGN-captured virus to T cells. As candidate microbicides should not interfere with the normal human microbiota, we examined the effect of CBAs against Lactobacillus strains, including a variety of vaginal strains, a gastrointestinal strain and several non-human isolates. None of the CBAs included in our studies inhibited the growth of these bacteria in several media, affected their viability or had any significant impact on their adhesion to HeLa cell monolayers.
  
  
  CONCLUSIONS
  The CBAs in this study were inhibitory to HIV-1 in several in vitro infection and transmission models, and may therefore qualify as potential microbicide candidates. The lack of significant impact on commensal vaginal lactobacilli is an important property of these CBAs in view of their potential microbicidal use.
authors: Centre of Microbial and Plant Genetics, KU Leuven, Kasteelpark Arenberg 20, bus 2460, B-3001 Leuven, Belgium.
authors: Mariya I
authors: MI
authors: Petrova
authors: Leen
authors: L
authors: Mathys
authors: Sarah
authors: S
authors: Lebeer
authors: Sam
authors: S
authors: Noppen
authors: Els J M
authors: EJ
authors: Van Damme
authors: Haruo
authors: H
authors: Tanaka
authors: Yasuhiro
authors: Y
authors: Igarashi
authors: Mario
authors: M
authors: Vaneechoutte
authors: Jos
authors: J
authors: Vanderleyden
authors: Jan
authors: J
authors: Balzarini
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D005260:Female; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007778:Lactobacillus / Q000187:drug effects*; D037102:Lectins / Q000494:pharmacology*; D014621:Vagina / Q000382:microbiology*
chemical_list: D019380:Anti-HIV Agents; D037102:Lectins
keywords: HIV/AIDS; adhesion; antimicrobial agents; antiretroviral therapy; bacterial biofilms; lactic acid bacteria; microbicides