Human immunodeficiency virus type 1 infection of the nervous system: Pathogenetic mechanisms

Leon G. Epstein, Howard Eliot Gendelman

Research output: Contribution to journalArticle

329 Citations (Scopus)

Abstract

Human immunodeficiency virus type 1 (HIV‐1) infection of the central nervous system is associated with characteristic virological, clinical, and neuropathological findings in adults and children. Productive infection in the brain and spinal cord occurs in blood‐derived macrophages, resident microglia, and multinucleated giant cells. Previous work implicated indirect mechanisms for neurotoxicity by HIV‐1 gene products or by factors secreted from HIV‐1‐infected macrophages. However, this cannot explain the paradox between the small numbers of infected cells and the widespread tissue pathology. Based on recent studies from our laboratories, we suggest that HIV‐1‐infected macrophages can initiate neurotoxicity, which is then amplified through cell‐to‐cell interactions with astrocytes. Macrophageastrocyte interactions produce cytokines tumor necrosis factor‐α and interleukin‐1b̃ and arachidonic metabolites that cause astroglial proliferation and neuronal injury. Inevitably, the astrogliosis serves to amplify these cellular processes while brain infection maintains itself in macrophage and microglia and possibly in astrocytes (by restricted infection). These findings, taken together, provide fresh insights into how low numbers of productively infected cells could elicit progressive and devastating neurological impairment during HIV‐1 disease, and suggest therapeutic strategies to interrupt the pathological process.

Original languageEnglish (US)
Pages (from-to)429-436
Number of pages8
JournalAnnals of Neurology
Volume33
Issue number5
DOIs
StatePublished - May 1993

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Virus Diseases
Nervous System
HIV-1
Macrophages
Microglia
Astrocytes
Infection
Human Immunodeficiency Virus Proteins
Brain
Pathologic Processes
Giant Cells
Spinal Cord
Central Nervous System
Tumor Necrosis Factor-alpha
Cell Count
Pathology
Cytokines
Wounds and Injuries
Therapeutics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Human immunodeficiency virus type 1 infection of the nervous system : Pathogenetic mechanisms. / Epstein, Leon G.; Gendelman, Howard Eliot.

In: Annals of Neurology, Vol. 33, No. 5, 05.1993, p. 429-436.

Research output: Contribution to journalArticle

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