Abstract
Both host and viral factors play an important role in the pathogenesis of human immunodeficiency virus (HIV)-associated bran injury. In this study, the authors examined the interactions between tumor necrosis factor (TNF)-α, CXCR4, the alpha chemokine receptor, and three HIV isolates, including the T-tropic viruses, HIV-1MN and HIV-1IIIB, and the dual tropic virus, HIV-189.6. The authors show by flow cytometry that treatment of differentiated SK-N-MC cells with TNF-α induces a significant increase in the cell surface expression of CXCR4 in a time- and dose-dependent manner. The effect is partly regulated at the level of transcription. To assess the biological significance of this finding, we show that TNF-α potentiates the ability of the above mentioned HIV isolates to induce neuronal apoptosis and that the effect is significantly reduced by pretreating cells with monoclonal antibodies to either CXCR4 and TNF-α. Together these results suggest that TNF-α may render neuronal cells vulnerable to the apoptotic effects of HIV by increasing the cell surface expression of CXCR4 and thus identify another mechanism by which TNF-α contributes to the pathogenesis of HIV-associated brain injury. Journal of NeuroVirology (2005) 11, 247–255.
This work was supported by R01 NS 36524 (BN), Lifespan—Tufts-Brown Center for AIDS Research Development Award BN), New England Medical Research Foundation (BN), and F32 NS10867 (KR). The authors thank HanneWaibel for excellent secretarial assistance.
