HIV-1 Tat toxin

This chapter summarizes the findings and the current understanding of the mechanism(s) underlying Tat-induced toxicity. Tat is one of the early viral proteins that is expressed during virus replication and is known to play a crucial role in promoting virus replication by transactivating the promoter region of the virus. To date, there is no effective treatment that blocks Tat activity. Both cell culture systems and murine animal models have provided valuable tools to explore the role of HIV-1 Tat in the pathogenesis of HIV-associated neurodegenerative disease (HAND). In resource-limiting settings, drug abuse, lack of availability of antiretrovirals and perinatal transmission of HIV-1 are major causes of AIDS in children. In such a setting, Tat toxicity could have serious deleterious effects in both the developing fetus and the newborn. HIV Tat has diverse but often deleterious effects on various cell types of the central nervous system (CNS). In the CNS, it can activate monocytes, astrocytes and microglia, which, in turn, leads to a “cytokine/chemokine storm” in the CNS. HIV-1 Tat not only exerts direct toxicity on the neurons, but can also indirectly lead to neuronal apoptosis, via the mediators released from other neighboring cells. These complex cascades of events could be self-propelling, thereby perpetuating a continuum of inflammatory responses in the brain of HIV-1-infected individuals.