title: Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells.
abstract: BACKGROUND
  The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route.
  
  
  RESULTS
  Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+) and BeWo-CD4+ (CD4+, CCR5+, CXCR4+) cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted.
  
  
  CONCLUSIONS
  Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.
authors.affiliation: Institut Pasteur, Unit of Regulation of Retroviral Infections, Department of Virology, 25 rue du Docteur Roux, Paris, France. anna-laura.ross@pasteur.fr
authors.forename: Anna Laura
authors.initials: AL
authors.lastname: Ross
authors.forename: Claude
authors.initials: C
authors.lastname: Cannou
authors.forename: Françoise
authors.initials: F
authors.lastname: Barré-Sinoussi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Menu
mesh_terms: D002460:Cell Line; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D014327:Trophoblasts / Q000821:virology*; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex