Mitogen-Activated Protein Kinase p38 in HIV Infection and Associated Brain Injury

Infection with human immunodeficiency virus-1 (HIV-1) often leads to HIV-associated neurocognitive disorders (HAND) prior to the progression to acquired immunodeficiency syndrome (AIDS). At the cellular level, mitogen-activated protein kinases (MAPK) provide a family of signal transducers that regulate many processes in response to extracellular stimuli and environmental stress, such as viral infection. Recently, evidence has accumulated suggesting that p38 MAPK plays crucial roles in various pathological processes associated with HIV infection, ranging from macrophage activation to neurotoxicity and impairment of neurogenesis to lymphocyte apoptosis. Thus, p38 MAPK, which has generally been linked to stress-related signal transduction, may be an important mediator in the development of AIDS and HAND.