Novel mechanisms of central nervous system damage in HIV infection

Abstract

Human immunodeficiency virus-1 infection of the central nervous system is an early event after primary infection, resulting in motor and cognitive defects in a significant number of individuals despite successful antiretroviral therapy. The pathology of the infected brain is characterized by enhanced leukocyte infiltration, microglial activation and nodules, aberrant expression of inflammatory factors, neuronal dysregulation and loss, and blood–brain barrier disruption. Months to years following the primary infection, these central nervous system insults result in a spectrum of motor and cognitive dysfunction, ranging from mild impairment to frank dementia. The mechanisms that mediate impairment are still not fully defined. In this review we discuss the cellular and molecular mechanisms that facilitate impairment and new data that implicate intercellular communication systems, gap junctions and tunneling nanotubes, as mediators of human immunodeficiency virus-1 toxicity and infection within the central nervous system. These data suggest potential targets for novel therapeutics.

Keywords:

• AIDS
• dementia
• inflammation
• gap junctions
• nanotubes
• chemokines

Acknowledgements

We are grateful to Dr. Brad Poulos and the Human Fetal Tissue Repository and the Analytical Imaging Facilities at the Albert Einstein College of Medicine. This work was supported by the National Institutes of Mental Health grants MH070297, MH075679, and MH083497 to JWB, NIH Centers for AIDS Research Grant AI-051519, a KO1 grant from the National Institutes of Mental Health (MH076679) to EAE, MSTP Training Grant 5 T32 GM007288 and the HIV-AIDS and Opportunistic Infections Institutional Training Grant T32 AI-007501 to JEH.

Disclosures

The authors report no conflicts of interest in this work.