Levels of human immunodeficiency virus type 1 (HIV-1) replication in macrophages determines the severity of murine HIV-1 encephalitis

Adeline Nukuna, Howard E. Gendelman, Jenae Limoges, Jennifer Rasmussen, Larisa Poluektova, Anuja Ghorpade, Yuri Persidsky

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The presence of specific neuroinvasive strains and necessity for brain viral replication for disease progression remain controversial issues in neuro-AIDS research. To investigate these questions, the authors injected human monocyte-derived macrophages (MDMs) infected with diverse viral strains were injected into the caudate and putamen of severe combined immunodeficient (SCID) mice. Independent of viral strain, infected MDMs became immunologically activated and elicited profound inflammatory reactions in brain areas most affected in humans. The intensity of neuropathologic changes, including microglial reactions, paralleled levels of viral infection and numbers of infected MDMs. The data suggest that HIV-1-associated neurological disease is related to the level of productive viral infection in activated macrophages. Virus infection, per se, may affect the ability of macrophages to respond to immune stimuli by overproduction of proinflammatory factors and neurotoxins, leading to neuronal dysfunction.

Original languageEnglish (US)
Pages (from-to)82-90
Number of pages9
JournalJournal of neurovirology
Volume10
Issue numberSUPPL. 1
DOIs
StatePublished - 2004

Keywords

  • Animal model
  • Encephalitis
  • HIV-1
  • Viral strain

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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