Effects of HIV-1-induced CD1c and CD1d modulation and endogenous lipid presentation on CD1c-restricted T-cell activation.
BACKGROUND
It has been shown that human immunodeficiency virus (HIV)-1 infection induces the production of endogenous lipids required for effective viral production, and the cluster of differentiation (CD)1 molecule CD1d is downregulated by HIV-1 infection. However, the role of endogenous lipid presentation and the implications of CD1 downregulation by HIV-1 infection have not yet been characterized.


RESULTS
In this study, we observed downregulation of both CD1c and CD1d expression through a Vpu-dependent and Nef-independent mechanism, and the concomitant HIV-1-induced production of host cholesterol decreased the extent of CD1c and CD1d modulation. While the modest downregulation of CD1c by HIV-1 infection decreased the ability of CD1c-restricted T cells to respond and secrete interferon-γ, the cholesterol upregulation in the same cells by HIV-1 infection appears to limit the downregulation of CD1c.


CONCLUSIONS
The two conflicting HIV-1-mediated changes in CD1c expression appear to minimize the modulation of CD1c expression, thus leading the host to maintain a CD1c-restricted T-cell response against HIV-1.
HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
Halonna
H
Kelly
Rajakumar
R
Mandraju
Jordana G A
JG
Coelho-dos-Reis
Moriya
M
Tsuji
D017951:Antigen Presentation / Q000276:immunology; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation; D006023:Glycoproteins / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D010713:Phosphatidylcholines / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism; D000086082:Viroporin Proteins
D018949:Antigens, CD1; D055610:Antigens, CD1d; D002784:Cholesterol; D006023:Glycoproteins; D054298:Human Immunodeficiency Virus Proteins; D007371:Interferon-gamma; D010713:Phosphatidylcholines; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C437944:CD1C protein, human; C526877:CD1D protein, human; C514837:nef protein, Human immunodeficiency virus 1; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins