Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells.
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.
Ross
Anna Laura
AL
Institut Pasteur, Unit of Regulation of Retroviral Infections, Department of Virology, 25 rue du Docteur Roux, Paris, France. anna-laura.ross@pasteur.fr
Cannou
Claude
C
Barré-Sinoussi
Françoise
F
Menu
Elisabeth
E
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
D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex