Lipopolysaccharide-induced HIV-1 expression in transgenic mice is mediated by tumor necrosis factor-alpha and interleukin-1, but not by interferon-gamma nor interleukin-6.
AIDS
; 14(10): 1299-307, 2000 Jul 07.
Article
in En
| MEDLINE
| ID: mdl-10930143
ABSTRACT
BACKGROUND:
As serum HIV-1 load correlates well with the prognosis of the disease, it is suggested that the viral load is one of the major determinants of the disease progression of AIDS. Accordingly, HIV-1 activation mechanisms were extensively studied in vitro, and involvement of cytokines including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6 and interferon (IFN)-gamma has been suggested in this process. However, so far the roles of these cytokines in the HIV-1 expression in vivo have not been well elucidated because of the lack of appropriate animal disease models.OBJECTIVE:
To elucidate the roles of cytokines in HIV-1 activation in vivo. DESIGN ANDMETHODS:
Transgenic mice carrying a defective HIV-1 genome were used as a model for HIV-1 carriers. In order to examine the possible involvement of cytokines in HIV-1 expression, TNF-alpha-, IL-1-, IL-6- and IFN-gamma-deficient HIV-1 transgenic mice, were produced and HIV-1 expression was analyzed after activation with bacterial lipopolysaccharides (LPS).RESULTS:
HIV-1 expression in the transgenic mouse spleen was activated 10- to 20-fold by LPS, and the serum p24 Gag protein levels reached 400 pg/ml, which is nearly equal to the levels that occur in AIDS patients. However, this augmentation was suppressed by 60% in TNF-alpha-deficient mice and by 40% in IL-1alpha/beta-deficient mice. In contrast, no suppression was observed in either IL-6-, IFN-gamma-, IL-1alpha, or IL-1beta-deficient mice.CONCLUSIONS:
Results suggest that TNF-alpha and IL-1 play important roles in HIV-1 gene activation and selective suppression of these cytokines could improve clinical prognosis and potentially slow progression of the disease.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytokines
/
HIV-1
Type of study:
Prognostic_studies
Language:
En
Journal:
AIDS
Journal subject:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Year:
2000
Document type:
Article
Affiliation country:
Japón
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM