Neuronal apoptosis induced by HIV-1 Tat protein and TNF-α: potentiation of neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia

Macrophages and HIV-1: dangerous liaisons

“…Several in vitro studies have shown that EAAT expression and function in astrocytes are reduced by HIV, probably due to the effects of inflammatory mediators and viral proteins (Dreyer and Lipton, 1995;Fine et al, 1996;Kort, 1998;Patton et al, 2000;Vesce et al, 1997). These findings (VallatDecouvelaere et al, 2003) support the hypothesis that in HIV infection, besides their classical neurotoxic properties involving glutamate-related excitotoxicity (Jiang et al, 2001) and oxidative stress (Mollace et al, 2001;Shi et al, 1998), activated microglia play a counterbalancing neuroprotective role by clearing extracellular glutamate and producing the anti-oxidant glutathione (Rimaniol et al, 2000;Rimaniol et al, 2001). …”

HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation

“…Earlier studies report that Tat, a potent stimulator of the cellular neurotoxic proteins such as TNFa gene (Sastry et al, 1990;Chen et al, 1997), exhibits the ability to cause neuronal cell damage and apoptosis through mechanisms that are independent of TNFa pathway (Merrill et al, 1992;Chen et al, 1997;Shi et al, 1998). In addition to its proapoptotic properties, an increasing number of reports ascribed a role for Tat in enhancing cell proliferation (Lotz et al, 1994;Cantaluppi et al, 2001).…”

HIV-1 Tat increases cell survival in response to cisplatin by stimulating Rad51 gene expression

“…In addition, Tat has been shown to alter several key host regulatory events by affecting the expression of various cytokines and immunomodulators such as TNFa, IL-2, and TGFb, which accelerate the viral infection cycle (Buonaguro et al, 1992;Chen et al, 1997;Sawaya et al, 1998;Rappaport et al, 1999;Gonzalez et al, 2001). These events can have a drastic effect on host cells and cause a variety of morphological metabolic changes that, in some cases, steer cells toward an apoptotic pathway (McCloskey et al, 1997;Shi et al, 1998). Of interest, some of these events may occur in uninfected cells upon their exposure to Tat secreted by infected cells (Rautonen et al, 1994;Rappaport et al, 1999).…”