Interactions of human immunodeficiency virus‐1 proteins with neurons: possible role in the development of human immunodeficiency virus‐1‐associated dementia

Abstract

Human immunodeficiency virus-1 (HIV-1)-associated dementia is a severe neurological complication of HIV-1 infection that affects 15-20% of the patients in the late stages of acquired immunodeficiency syndrome. HIV-1-associated dementia is most probably a consequence of HIV-1 infection of the brain rather than of an opportunistic pathogen. The exact mechanism by which the virus causes this disorder, however, is not completely understood. A number of HIV-1 proteins have been shown to be released from HIV-1-infected cells and / or to be present in the extracellular milieu in the HIV-1-infected brain. Moreover, these proteins have been shown to posses neurotoxic and / or neuromodulatory features in vitro . This review describes the possible direct interactions of the HIV-1 proteins gp120, gp41, vpr, tat, rev, vpu and nef with neurons, which might play a role in the development of HIV-1-associated dementia in vivo .Keywords Acquired immunodeficiency, human immunodeficiency virus-1-associated dementia, human immunodeficiency virus-1 proteins, neurons, neurotoxicity.

Cell death in HIV dementia

“…in astrocytes) and Tat may be actively released into the extracellular environment. 21 Some of the structural and regulatory proteins have been shown to cause neuronal dysfunction and/or death and thus may be referred to as virotoxins (Table 1).…”

“…For example, exposure of astrocytes to Tat induces them to produce MCP-1, and MCP-1 is elevated in the brain tissue and CSF of HIV-1 dementia patients. 21 Inoculation of HIV-infected monocytes into the basal ganglia and cortex of severe combined immunodeficiency disease (SCID) mice results in pathological features similar to those of human HIV-1 dementia. In such SCID/HIV-1 mice, the expression of TNFa, IL-6 and vascular endothelial growth factor (VEGF) was increased.…”

Protecting neurons from HIV-1 gp120-induced oxidant stress using both localized intracerebral and generalized intraventricular administration of antioxidant enzymes delivered by SV40-derived vectors

“…HIV-1 infects resident microglia, periventricular macrophages and some astrocytes, 8 leading to increased production of cytokines, such as interleukin-6, interleukin-1b and tumor necrosis factor-a, and chemokines such as monocyte chemoattractant protein-1 (MCP-1). 9 Microglia and macrophages also release HIV-1 proteins, several of which are neurotoxins: envelope (Env) proteins gp120 and gp41, and the nonstructural proteins Tat, Nef, Vpr and Rev.…”

Antiviral Efficacy of the Novel Compound BIT225 against HIV-1 Release from Human Macrophages

“…The authors of the study suggest that persistent viremia during antiretroviral therapy is likely to be derived from reservoirs of long-lived virus-producing cells that are not affected by currently available drugs that target new cycles of viral replication. Lastly, infiltration by infected macrophages is the major route of infection of the central nervous system, causing HIV-1-associated AIDS dementia in 15 to 20% of late-stage AIDS patients (41). The poor penetration of some antiretroviral drugs into the cerebrospinal fluid may result in the development of a sanctuary site, where macrophages, in addition to microglial cells, can result in persistent viremia.…”