title: Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis.
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.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
authors.forename: Santhi
authors.initials: S
authors.lastname: Gorantla
authors.forename: Edward
authors.initials: E
authors.lastname: Makarov
authors.forename: Jennifer
authors.initials: J
authors.lastname: Finke-Dwyer
authors.forename: Antonio
authors.initials: A
authors.lastname: Castanedo
authors.forename: Adelina
authors.initials: A
authors.lastname: Holguin
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Gebhart
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Larisa
authors.initials: L
authors.lastname: Poluektova
mesh_terms: D015526:AIDS Dementia Complex / Q000209:etiology* / Q000473:pathology / Q000821:virology; D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D008587:Meningitis, Viral / Q000150:complications; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic
chemical_list: C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit