Signal Transduction in HIV Protein-Treated Astrocytes

Astrocytes, the most abundant cells of the CNS are believed to play vital roles in brain development and functioning, providing trophic support to neurons and eliciting CNS responses to pathogens/injury. During HIV infection of the CNS, glial activation and infection play major roles in generating the immune activation, a process which, in turn, leads to release of neurotoxic mediators (viral and cellular). Accompanying the activation and proliferation of astroglia is also recruitment of mononuclear phagocytes across the endothelium. Regulated signal transduction pathways finely control all these processes. While earlier believed to support only abortive HIV infection, astrocytes are now recognized to be active participants of productive viral replication. Following infection and/or exposure to viral proteins released from neighboring infected cells, astrocytes become activated and elicit release of inflammatory mediators, such as cytokines, chemokines and growth factors, that are toxic not only for neurons but also for neighboring cells around astrocytes within the CNS. This cascade of inflammation triggers the ensuing neuropathogenesis associated with HIV-1. The normally neuroprotective role of astrocytes thus transforms into a functionally deleterious function, with the ultimate result of disrupted CNS homeostasis. The current review is an attempt to summarize the cellular signal transduction pathways critical for astrocyte activation and inflammation involved in HIV-1 associated dementia.