HIV-1 Nef-induced upregulation of DC-SIGN in dendritic cells promotes lymphocyte clustering and viral spread.

Nathalie Sol-Foulon (1) , Arnaud Moris (1) , Cinzia Nobile (1) , Claire Boccaccio (2) , Anneke Engering (3) , Jean-Pierre Abastado (2) , Jean-Michel Heard (1) , Yvette van Kooyk (3) , Olivier Schwartz (1)

1 Rétrovirus et Transfert Génétique
2 IDM - LUTI - IDM Laboratoire Universitaire de Transfert en Immunologie (Luti)
3 Department of Molecular Cell Biology

DC-SIGN, a dendritic cell (DC)-specific lectin, mediates clustering of DCs with T lymphocytes, a crucial event in the initiation of immune responses. DC-SIGN also binds HIV envelope glycoproteins, allowing efficient virus capture by DCs. We show here that DC-SIGN surface levels are upregulated in HIV-1-infected DCs. This process is caused by the viral protein Nef, which acts by inhibiting DC-SIGN endocytosis. Upregulation of DC-SIGN at the cell surface dramatically increases clustering of DCs with T lymphocytes and HIV-1 transmission. These results provide new insights into how HIV-1 spreads from DCs to T lymphocytes and manipulates immune responses. They help explain how Nef may act as a virulence factor in vivo.

Domains: Life Sciences [q-bio]

Nathalie Sol-Foulon, Arnaud Moris, Cinzia Nobile, Claire Boccaccio, Anneke Engering, et al.. HIV-1 Nef-induced upregulation of DC-SIGN in dendritic cells promotes lymphocyte clustering and viral spread.. Immunity, 2001, 16 (1), pp.145-55. ⟨10.1016/S1074-7613(02)00260-1⟩. ⟨pasteur-01107753⟩