Retrovirology: Research and Treatment

Neurophysiology laboratory, the Center for Neurovirology and Neurodegenerative Disorders, and Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, U.S.A.

Abstract

HIV-1-associated dementia (HAD) describes the cognitive impairments and behavioral disturbances which afflict many HIV-infected individuals. Although the incidence of HAD has decreased significantly in the era of HAART, it remains a significant complication of HIV-1 infection as patients with acquired immune deficient syndrome (AIDS) live longer, antiretroviral drugs remain unable to effectively cross the blood-brain barrier (BBB), and HIV-1 resistance grows due to viral strain mutation. Although the precise mechanism leading to HAD is incompletely understood, it is commonly accepted its progression involves a critical mass of infected and activated mononuclear phagocytes (MP; brain perivascular macro- phages and microglia) releasing immune and viral products in brain. These cellular and viral products induce neuronal dysfunction and injury via various signaling pathways. Emerging evidence indicates that voltage-gated potassium (K_v) channels, key regulators of cell excitability and animal behavior (learning and memory), are involved in the pathogenesis of HAD/HAND. Here we survey the literature and find HAD related alterations in cellular and viral products can alter MP and neuronal K_v channel activity, leading to MP and neuronal dysfunction and cognitive deficits. Thus, MP and neuronal K_v channels may be a new target in the effort to develop therapies for HAD and perhaps other inflammatory neurodegenerative disorders.