Impact of HIV on Regional & Cellular Organisation of the Brain

Abstract

There are many excellent reviews of HIV infection of the nervous system. However these all assume that the reader has a working knowledge of the structure and cellular architecture of the brain. It may be that specialised brain vocabulary represents an unwelcome hurdle for those scientists with expert knowledge of the effects of HIV in other cell systems and who wish to extend that interest to the brain. This review provides an introduction to the component structures and cells of the brain and an overview of their involvement in HIV/AIDS. HIV infection leads to death through its capacity to progressively devastate the immune system. Current anti-HIV therapy has achieved considerable success in halting and partially reversing this process. In the absence of treatment, the breakdown of immunity is marked by declining CD4 counts and increasing vulnerability to opportunistic infections. In parallel with these effects on the lymphoid system, the nervous system is frequently the site of an initially stealthy infection which leads ultimately to symptomatic disease in a significant proportion of HIV infected individuals. The most feared manifestation of central nervous system (CNS) involvement is dementia. Unfortunately, serial CD4 counts and measurement of blood viral load do not serve to identify or monitor early infection of brain tissue. Since effective anti-HIV therapy has not achieved eradication of virus from lymphoid tissues, and anti-HIV drugs do not enter the nervous system easily, it is hardly surprising that HIV infection of the nervous system continues to cause clinical problems. Even in treatment-compliant patients, a measurable degree of cognitive impairment may develop, signalling previous or present HIV-related brain injury. The cause of HIV associated dementia and cognitive disability remains poorly understood. Perhaps most significantly, the long-term consequences of clinically occult brain infection are unknown and will require further investigation.

Neurobehavioral Performance in Feline Immunodeficiency Virus Infection: Integrated Analysis of Viral Burden, Neuroinflammation, and Neuronal Injury in Cortex

“…In fact, the results of the present studies suggest that the impairment observed in FIV-infected animals is not merely developmental delay but actually due to ongoing neurodegeneration because the FIV-infected group exhibit a sustained worsening in performance over time (12 and 15 weeks after infection). Of interest, the parietal cortex is adversely affected by HIV infection, as evidenced by neuroinflammation and neuronal loss, similar to the present findings (Bell et al, 2006). The object memory task is a cortical measure of neurobehavioral function and was the most robust task in distinguishing FIVϪ from FIVϩ animals.…”

Doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) as an HIV/neuroAIDS model

“…Astrogliosis or increased GFAP expression in astrocytes is one of the very few consistent hallmarks of HIV-1 infection of the CNS (Bell et al 2006a; Price 1996). Astrocytes have a variety of functions, many of which are related to the CNS homeostasis [see reviews (Barres 1991; Eddleston and Mucke 1993)].…”

Morphine Exacerbates HIV-1 Tat-Induced Cytokine Production in Astrocytes through Convergent Effects on [Ca2+]i, NF-κB Trafficking and Transcription

“…Among human immunodeficiency virus type 1 (HIV-1)-infected individuals, injection drug users are at greater risk than nonusers of developing HIV-associated neurological impairment, as well as other opportunistic infections [1]–[3]. Not only does injection drug use provide a mode for viral spread, but the opioid system (i.e., endogenous opioid peptides and receptors) also plays a fundamental role in modifying, and in many cases exacerbating the pathogenesis of neuro-acquired immune deficiency syndrome (neuroAIDS) [4]–[6].…”