HIV-1 NEF protein
| FUNCTION |
Nef expression promotes virion infectivity. It acts by preventing transport to plasma membrame of several host cellular proteins.
- Nef induces the endocytosis of MHC-I molecules. When a cell is infected, foreign antigens associate with MHC-I molecules and are recognized by and induce the cytotoxic T lymphocytes (CTLs) immune response and cell lysis . Nef binds to the clathrin adaptor protein-1 (AP-1) and MHC-I to form a stable complex that allows AP-1 to direct MHC-I endocytosis and degradation. Nef reduces MHC-I at the cell surface but synthesis and presense of MHC-I at the ER and Golgi apparatus occur normally .
- Nef downregulates CD4. Nef binds to AP-2 and hijacks AP-dependent trafficking pathways for CD4 downregulation . The interaction between Nef and AP-2 forms a stable complex with surface CD4 molecules and induces the endocytosis and lysomal degradation of CD4.
- Nef binds to and modulates T-cell antigen receptor (TCR) signalling .
- Nef promotes exclusion of SERINC5 and SERINC3 from virion incorporation , thereby preventing the negative effect of these host proteins on virion infectivity.
| INTERACTIONS |
CD4, ALIX, AP1M1, AP2M1, MHC-I, ACOT8, PACS-1, PACS-2, PAK2, LCK, HCK, ABCA1 and Calnexin
| SUBCELLULAR LOCATION |
| TIMING OF EXPRESSION |
Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein
O. Schwartz, V. Mar?chal, S. Le Gall, F. Lemonnier, J. M. Heard
Nat. Med. March 1996; 2: 338-342
HIV-1 accessory proteins adapt cellular adaptors to facilitate immune evasion
David R. Collins, Kathleen L. Collins
PLoS Pathog. January 2014; 10: e1003851
Identification of a novel binding site between HIV type 1 Nef C-terminal flexible loop and AP2 required for Nef-mediated CD4 downregulation
Yong-Jiu Jin, Catherine Yi Cai, Mihaly Mezei, Michael Ohlmeyer, Roberto Sanchez, Steven J. Burakoff
AIDS Res. Hum. Retroviruses April 2013; 29: 725-731
Nef-arious goings-on at the Golgi
James H. Hurley, Juan S. Bonifacino
Nat. Struct. Mol. Biol. July 2012; 19: 661-662
HIV-1 Nef: a multifaceted modulator of T cell receptor signaling
Libin Abraham, Oliver T. Fackler
Cell Commun. Signal 2012; 10: 39
HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation
Annachiara Rosa, Ajit Chande, Serena Ziglio, Veronica De Sanctis, Roberto Bertorelli, Shih Lin Goh, Sean M. McCauley, Anetta Nowosielska, Stylianos E. Antonarakis, Jeremy Luban, Federico Andrea Santoni, Massimo Pizzato
Nature October 8, 2015; 526: 212?217