Systemic HIV-1 infection produces a unique glial footprint in humanized mouse brains

Disease Models & Mechanisms
Weizhe LiLarisa Poluektova

Abstract

Studies of innate glial cell responses for progressive human immunodeficiency virus type one (HIV-1) infection are limited by a dearth of human disease-relevant small-animal models. To overcome this obstacle, newborn NOD/SCID/IL2Rγc-/- (NSG) mice were reconstituted with a humanized brain and immune system. NSG animals of both sexes were transplanted with human neuroglial progenitor cells (NPCs) and hematopoietic stem cells. Intraventricular injection of NPCs symmetrically repopulated the mouse brain parenchyma with human astrocytes and oligodendrocytes. Human glia were in periventricular areas, white matter tracts, the olfactory bulb and the brain stem. HIV-1 infection led to meningeal and perivascular human leukocyte infiltration into the brain. Species-specific viral-neuroimmune interactions were identified by deep RNA sequencing. In the corpus callosum and hippocampus of infected animals, overlapping human-specific transcriptional alterations for interferon type 1 and 2 signaling pathways (STAT1, STAT2, IRF9, ISG15, IFI6) and a range of host antiviral responses (MX1, OAS1, RSAD2, BST2, SAMHD1) were observed. Glial cytoskeleton reorganization, oligodendrocyte differentiation and myelin ensheathment (MBP, MOBP, PLP1, MAG, ZNF4...Continue Reading

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Citations

Aug 22, 2018·Nanomedicine·Midhun B ThomasSanthi Gorantla
Jan 27, 2019·Cell Death and Differentiation·Vatsal SachanNabil G Seidah
Jan 23, 2020·Current HIV/AIDS Reports·Jay TrivediSiddappa N Byrareddy
May 11, 2020·Cell Stem Cell·Peng JiangRanjie Xu

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Methods Mentioned

BETA
Fluorescence-activated cell sorting
ELISA
PCR
dissection
flow cytometry
RNA-seq
leukapheresis

Software Mentioned

FACS
Cufflinks
fqtrim
DEFINIENS Tissue Studio
TopHat
GeneCards
Cuffdiff
Tuxedo RNA - tool
FLOWJO

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