Lipopolysaccharide-induced HIV-1 expression in transgenic mice is mediatedby tumor necrosis factor-alpha and interleukin-1, but not by interferon-gamma nor interleukin-6
J. Tanaka et al., Lipopolysaccharide-induced HIV-1 expression in transgenic mice is mediatedby tumor necrosis factor-alpha and interleukin-1, but not by interferon-gamma nor interleukin-6, AIDS, 14(10), 2000, pp. 1299-1307
Background: As serum HIV-1 load correlates well with the prognosis of the d
isease, it is suggested that the viral load is one of the major determinant
s of the disease progression of AIDS. Accordingly, HIV-1 activation mechani
sms were extensively studied in vitro, and involvement of cytokines includi
ng tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6 and interfer
on (IFN)-gamma has been suggested in this process. However, so far the role
s of these cytokines in the HIV-1 expression in vivo have not been well elu
cidated because of the lack of appropriate animal disease models.
Objective: To elucidate the roles of cytokines in HIV-1 activation in vivo.
Design and methods: Transgenic mice carrying a defective HIV-1 genome were
used as a model for HIV-1 carriers. In order to examine the possible involv
ement of cytokines in HIV-1 expression, TNF-alpha-, IL-1- IL-6- and IFN-gam
ma-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, t
his augmentation was suppressed by 60% in TNF-alpha-deficient mice and by 4
0% in IL-1 alpha/beta-deficient mice. In contrast, no suppression was obser
ved in either IL-6-, IFN-gamma-, IL-1 alpha, or IL-1 beta-deficient mice.
Conclusions: Results suggest that TNF-alpha and IL-1 play important roles i
n HIV-1 gene activation and selective suppression of these cytokines could
improve clinical prognosis and potentially slow progression of the disease.
(C) 2000 Lippincott Williams & Wilkins.