Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients.

Abstract

Dysfunction of the central nervous system (CNS) is a prominent feature of the acquired immune deficiency syndrome (AIDS). Many of these patients have a subacute encephalitis consistent with a viral infection of the CNS. We studied the brains of 12 AIDS patients using in situ hybridization to identify human immunodeficiency virus [HIV, referred to by others as human T-cell lymphotropic virus type III (HTLV-III), lymphadenopathy-associated virus (LAV), AIDS-associated retrovirus (ARV)] nucleic acid sequences and immunocytochemistry to identify viral and cellular proteins. Nine patients had significant HIV infection in the CNS. In all examined brains, the white matter was more severely involved than the grey matter. In most cases the infection was restricted to capillary endothelial cells, mononuclear inflammatory cells, and giant cells. In a single case with severe CNS involvement, a low-level infection was seen in some astrocytes and neurons. These results suggest that CNS dysfunction is due to indirect effects rather than neuronal or glial infection.

In vitro infection of aortic endothelial cells by caprine arthritis encephalitis virus enhances in vitro transmigration of peripheral blood leukocytes and modulates their phenotypic expression

“…It is not established at present whether or not CAEV infects endothelial cells in natural infections, although other lentiviruses such as HIV-1 do [16,26]. The modulation of the characteristics of leukocytes after transmigration that we observe could contribute to the evolution of local immune reactions.…”

EGCG mitigates neurotoxicity mediated by HIV-1 proteins gp120 and Tat in the presence of IFN-γ: Role of JAK/STAT1 signaling and implications for HIV-associated dementia

“…These cells seemingly serve as both viral factories and as mediators for inflammatory events resulting in neuropathology and subsequent neuropsychiatric impairment; the sequelae of HAD linked to "AIDS dementia-associated neuron damage" [1,14,23,31]. Indeed, pathologic CNS immune dysfunction has been widely explored in many past studies of microglia; the primary host cells for HIV-1 in the CNS [8,13,32,33]. In addition, considering that HIV-1 rarely infects neurons [17], many investigations have focused on neurotoxic effects of viral proteins including HIV-1 gp120 and Tat, acting in concert with proinflammatory circuits mediated by reactive immune cells and soluble factors able to induce or precipitate neuron death in HAD [31].…”

Contribution of Proteoglycans to Human Immunodeficiency Virus Type 1 Brain Invasion

“…The neuropathology associated with HIV-1 infection in the brain is characterized by widespread axonal damage, astrocytosis, myelin loss, and infiltration by bloodderived monocyte/macrophages, resident microglia, and multinucleated giant cells. The main target cells for HIV replication in the brain are macrophages and microglial cells (69,71,91). HIV-infected macrophages/microglia overproduce viral proteins, chemokines, and cytokines that induce dysfunction or apoptosis of neurons and astrocytes (reviewed in references 3, 5, 16, 18, 41, 44, 58, 85, and 98).…”