Specific Th1 cytokine down-regulation associated with primary clinically derived human immunodeficiency virus type 1 Nef gene-induced expression.
HIV-1 infection is associated with a progressive and functional decline in the CD4+ lymphoid Th1 subset. Here, we propose that the HIV nef gene product may function as a specific regulator of Th1 cytokine production. By use of a T cell-specific inducible expression system, we show that upon T cell activation, induced nef expression down-regulated both IL-2 and IFN-gamma production in a dose-dependent manner, whereas IL-4, IL-9, IL-13, IL-8, and TNF-alpha production remained unaffected. In addition to this, independent transfected clones expressing various nef genes, including nef sequences amplified directly from an HIV-1 primary clinical isolate, displayed a similar pattern of cytokine expression. The specific Th1 impairment induced by nef, therefore, seems to be an important and conserved feature of HIV-1 infection and may represent a significant function of this viral gene in AIDS pathogenesis.
Collette
Y
Y
Institut National de la Santé et de la Recherche Médicale U-119/Institut Paoli Calmette, Marseille, France.
Chang
H L
HL
Cerdan
C
C
Chambost
H
H
Algarte
M
M
Mawas
C
C
Imbert
J
J
Burny
A
A
Olive
D
D
D001483:Base Sequence; D018929:Cell Culture Techniques; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D015754:Genes, nef / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D018417:Th1 Cells / Q000378:metabolism*; D014162:Transfection
D007376:Interleukin-2; D007371:Interferon-gamma