The Nef protein of HIV-1 induces loss of cell surface costimulatory molecules CD80 and CD86 in APCs.
The Nef protein of HIV-1 is essential for its pathogenicity and is known to down-regulate MHC expression on infected cell surfaces. We now show that Nef also redistributes the costimulatory molecules CD80 and CD86 away from the cell surface in the human monocytic U937 cell line as well as in mouse macrophages and dendritic cells. Furthermore, HIV-1-infected U937 cells and human blood-derived macrophages show a similar loss of cell surface CD80 and CD86. Nef colocalizes with MHC class I (MHCI), CD80, and CD86 in intracellular compartments, and binds to both mouse and human CD80 and CD86. Some Nef mutants defective in MHCI down-modulation, including one from a clinical isolate, remain capable of down-modulating CD80 and CD86. Nef-mediated loss of surface CD80/CD86 is functionally significant, because it leads to compromised activation of naive T cells. This novel immunomodulatory role of Nef may be of potential importance in explaining the correlations of macrophage-tropism and Nef with HIV-1 pathogenicity and immune evasion.
Chaudhry
Ashutosh
A
National Institute of Immunology, New Delhi, India.
Das
Suman Ranjan
SR
Hussain
Amjad
A
Mayor
Satyajit
S
George
Anna
A
Bal
Vineeta
V
Jameel
Shahid
S
Rath
Satyajit
S
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism* / Q000821:virology; D018122:B7-1 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology; D015693:Gene Products, nef / Q000235:genetics / Q000502:physiology*; D015658:HIV Infections / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D020298:U937 Cells; D054311:nef Gene Products, Human Immunodeficiency Virus
D018122:B7-1 Antigen; D015693:Gene Products, nef; D015395:Histocompatibility Antigens Class I; D054311:nef Gene Products, Human Immunodeficiency Virus