AIDS dementia complex and HIV‐1 brain infection: Clinical‐virological correlations

Abstract

To evaluate the presence and distribution of central nervous system infection by human immunodeficiency virus type 1 (HIV-1), we used immunohistochemical methods to map the HIV-1 p24 core protein in the brains of 55 autopsied patients with acquired immunodeficiency syndrome (AIDS). In a subset of 40 of these patients who had undergone antemortem neurological evaluation of the AIDS dementia complex (ADC), we analyzed the relation between the severities of the viral infection and clinical dysfunction. Viral antigen was detected in macrophages and cells with morphological and immunohistochemical characteristics of microglia as well as multinucleated cells. The distribution of antigen-positive cells preferentially involved certain deep brain structures, especially the globus pallidus, other basal ganglia nuclei, and the central white matter. Overall, the presence and frequency of infected cells were highly correlated with the histological findings of multinucleated-cell encephalitis and in general with the clinical ADC stage. However, infection was often more limited than might be "anticipated" from the severity of patients' clinical dysfunction: Only 61% of patients with at least ADC stage 1 had detectable antigen and of these only approximately 30% of the brain sections were antigen positive. These results suggest a pathogenetic model of ADC where virus- or cell-coded toxins amplify the effect of limited brain infection.

Cytokine signals propagate through the brain

“…For example, IL-1 is elevated in cortex of individuals who died with AIDS 15 although the frequency of HIV-1-infected cells in the cortex is lower than in other regions. 16 Evidence reviewed here indicates that both central and systemic perturbations induce or upregulate IL-1 and TNF␣ expression and this 'cytokine signal' propagates through the parenchyma sometimes to distant regions that are apparently unconnected by neu- 17 (By 'perturbations' we mean central or systemic stimuli that alter IL-1 and TNF␣ expression.) We sought to identify the mechanism and pathways (ie physical substrates) of cytokine signal propagation within the brain.…”

Microglial and Astrocyte Chemokines Regulate Monocyte Migration through the Blood-Brain Barrier in Human Immunodeficiency Virus-1 Encephalitis

“…8,[43][44][45] MPs were grouped together, as a homogenous cell unit. The production of neurotoxins by microglia and brain macrophages was suggested as a major but indirect pathogenetic factor in HAD.…”

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

“…Postmortem studies have confirmed increased viral load [22,23] and vasculopathy [24] in basal ganglia structures, which further suggest direct damage to these structures during HIV infection. Avison et al [25] confirmed the presence of vasculopathy in vivo by examining intravenous contrast-enhanced MRI scans of HIV-infected patients.…”