Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis

Am J Pathol. 2010 Dec;177(6):2938-49. doi: 10.2353/ajpath.2010.100536. Epub 2010 Nov 18.


Few rodent models of human immunodeficiency virus type one (HIV-1) infection can reflect the course of viral infection in humans. To this end, we investigated the relationships between progressive HIV-1 infection, immune compromise, and neuroinflammatory responses in NOD/scid-IL-2Rγ(c)(null) mice reconstituted with human hematopoietic CD34(+) stem cells. Human blood-borne macrophages repopulated the meninges and perivascular spaces of chimeric animals. Viral infection in lymphoid tissue led to the accelerated entry of human cells into the brain, marked neuroinflammation, and HIV-1 replication in human mononuclear phagocytes. A meningitis and less commonly an encephalitis followed cM-T807 antibody-mediated CD8(+) cell depletion. We conclude that HIV-1-infected NOD/scid-IL-2Rγ(c)(null) humanized mice can, at least in part, recapitulate lentiviral neuropathobiology. This model of neuroAIDS reflects the virological, immunological, and early disease-associated neuropathological components of human disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Dementia Complex / etiology*
  • AIDS Dementia Complex / pathology
  • AIDS Dementia Complex / virology
  • Animals
  • Brain / immunology
  • Brain / virology
  • Cells, Cultured
  • Disease Models, Animal*
  • Disease Progression
  • HIV Infections / complications*
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Interleukin Receptor Common gamma Subunit / genetics
  • Meningitis, Viral / complications
  • Mice*
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic


  • Il2rg protein, mouse
  • Interleukin Receptor Common gamma Subunit