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

Santhi Gorantla, Edward Makarov, Jennifer Finke-Dwyer, Antonio Castanedo, Adelina Holguin, Catherine L Gebhart, Howard Eliot Gendelman, Larisa Y Poluektova

Research output: Contribution to journalArticle

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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- 2Rγcnull 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-2Rγcnull 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.

Original languageEnglish (US)
Pages (from-to)2938-2949
Number of pages12
JournalAmerican Journal of Pathology
Volume177
Issue number6
DOIs
StatePublished - Dec 2010

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HIV Infections
HIV-1
Virus Diseases
Meninges
Immune System Diseases
Lymphoid Tissue
Encephalitis
Phagocytes
Hematopoietic Stem Cells
Meningitis
Rodentia
Macrophages
HIV
Antibodies
Brain

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis. / Gorantla, Santhi; Makarov, Edward; Finke-Dwyer, Jennifer; Castanedo, Antonio; Holguin, Adelina; Gebhart, Catherine L; Gendelman, Howard Eliot; Poluektova, Larisa Y.

In: American Journal of Pathology, Vol. 177, No. 6, 12.2010, p. 2938-2949.

Research output: Contribution to journalArticle

Gorantla, Santhi ; Makarov, Edward ; Finke-Dwyer, Jennifer ; Castanedo, Antonio ; Holguin, Adelina ; Gebhart, Catherine L ; Gendelman, Howard Eliot ; Poluektova, Larisa Y. / Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis. In: American Journal of Pathology. 2010 ; Vol. 177, No. 6. pp. 2938-2949.
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