title: A glycomimetic compound inhibits DC-SIGN-mediated HIV infection in cellular and cervical explant models.
abstract: OBJECTIVE
  Dendritic cell-specific intercellular adhesion molecule (ICAM)-3 grabbing nonintegrin (DC-SIGN) participates in the initial stages of sexually transmitted HIV-1 infection by recognizing highly mannosylated structures presented in multiple copies on HIV-1 gp120 and promoting virus dissemination. Inhibition of HIV interaction with DC-SIGN thus represents a potential therapeutic approach for viral entry inhibition at the mucosal level.
  
  
  METHODS
  Herein we evaluate the efficacy in inhibiting HIV-1 infection and the potential toxicity of a multimeric glycomimetic DC-SIGN ligand (Dendron 12).
  
  
  METHODS
  The ability of Dendron 12 to block HIV-1 infection was assessed in cellular and human cervical explant models. Selectivity of Dendron 12 towards DC-SIGN and langerin was evaluated by surface plasmon resonance studies. β chemokine production following stimulation with Dendron 12 was also analyzed. Toxicity of the compound was evaluated in cellular and tissue models.
  
  
  RESULTS
  Dendron 12 averted HIV-1 trans infection of CD4(+) T lymphocytes in presence of elevated viral loads and prevented HIV-1 infection of human cervical tissues, under conditions mimicking compromised epithelial integrity, by multiple clades of R5 and X4 tropic viruses. Treatment with Dendron 12 did not interfere with the activity of langerin and also significantly elicited the production of the β chemokines MIP-1α, MIP-1β and RANTES.
  
  
  CONCLUSIONS
  Dendron 12 thus inhibits HIV-1 infection by competition with binding of HIV to DC-SIGN and stimulation of β-chemokine production. Dendron 12 represents a promising lead compound for the development of anti-HIV topical microbicides.
authors: Department of Clinical Sciences L. Sacco, University of Milan, Segrate, Italy.
authors: Angela
authors: A
authors: Berzi
authors: José J
authors: JJ
authors: Reina
authors: Roberta
authors: R
authors: Ottria
authors: Ieva
authors: I
authors: Sutkeviciute
authors: Patrizio
authors: P
authors: Antonazzo
authors: Macarena
authors: M
authors: Sanchez-Navarro
authors: Eric
authors: E
authors: Chabrol
authors: Mara
authors: M
authors: Biasin
authors: Daria
authors: D
authors: Trabattoni
authors: Irene
authors: I
authors: Cetin
authors: Javier
authors: J
authors: Rojo
authors: Franck
authors: F
authors: Fieschi
authors: Anna
authors: A
authors: Bernardi
authors: Mario
authors: M
authors: Clerici
mesh_terms: D000328:Adult; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000187:drug effects*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000276:immunology / Q000821:virology*; D019742:Chemokines, CC / Q000096:biosynthesis / Q000187:drug effects; D050091:Dendrimers / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006031:Glycosylation; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D037181:Lectins, C-Type / Q000187:drug effects* / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects*; D015728:Receptors, HIV / Q000235:genetics / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D000891:Anti-Infective Agents, Local; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019742:Chemokines, CC; D050091:Dendrimers; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D015728:Receptors, HIV; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C121916:CD207 protein, human