Activation of Human Microglial Cells by HIV-1 gp41 and Tat Proteins

The viral proteins, Tat (HIV-1 nuclear protein) and gp41 (HIV-1 coat protein), detected in the brains of HIV-1-infected patients have been shown to be neurotoxic. We investigated the effects of HIV-1 Tat and gp41 proteins on cytokine, chemokine, and superoxide anion (O−2) production by microglia, the resident macrophages of the brain. Tat and gp41 dose-dependently stimulated cytokine and chemokine production by microglia. Peak production of these cytokines and chemokines differed in microglial cells treated with gp41 and Tat. Expression of cytokine and chemokine mRNA was also stimulated in gp41- and Tat-treated microglia. Neither gp41 nor Tat alone stimulated O−2 production by microglia. Treatment of microglial cells with Tat but not with gp41 evoked an increase in intracellular Ca2+. The results of this study suggest that HIV-1 Tat and gp41 proteins impact several key functions of microglial cells which could contribute to the neuropathogenesis of HIV-1.