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Links between Progressive HIV-1 Infection of Humanized Mice and Viral Neuropathogenesis

Authors
Journal
American Journal Of Pathology
0002-9440
Publisher
Elsevier
Publication Date
Volume
177
Issue
6
Identifiers
DOI: 10.2353/ajpath.2010.100536
Keywords
  • Immunopathology And Infectious Diseases
Disciplines
  • Biology
  • Medicine

Abstract

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.

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