TY - JOUR
T1 - Links between progressive HIV-1 infection of humanized mice and viral neuropathogenesis
AU - Gorantla, Santhi
AU - Makarov, Edward
AU - Finke-Dwyer, Jennifer
AU - Castanedo, Antonio
AU - Holguin, Adelina
AU - Gebhart, Catherine L
AU - Gendelman, Howard E.
AU - Poluektova, Larisa
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
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U2 - 10.2353/ajpath.2010.100536
DO - 10.2353/ajpath.2010.100536
M3 - Article
C2 - 21088215
AN - SCOPUS:78650217622
SN - 0002-9440
VL - 177
SP - 2938
EP - 2949
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -