HIV infects astrocytes in vivo and egresses from the brain to the periphery

PLoS Pathogens
Victoria LutgenLena Al-Harthi

Abstract

HIV invades the brain during acute infection. Yet, it is unknown whether long-lived infected brain cells release productive virus that can egress from the brain to re-seed peripheral organs. This understanding has significant implication for the brain as a reservoir for HIV and most importantly HIV interplay between the brain and peripheral organs. Given the sheer number of astrocytes in the human brain and their controversial role in HIV infection, we evaluated their infection in vivo and whether HIV infected astrocytes can support HIV egress to peripheral organs. We developed two novel models of chimeric human astrocyte/human peripheral blood mononuclear cells: NOD/scid-IL-2Rgc null (NSG) mice (huAstro/HuPBMCs) whereby we transplanted HIV (non-pseudotyped or VSVg-pseudotyped) infected or uninfected primary human fetal astrocytes (NHAs) or an astrocytoma cell line (U138MG) into the brain of neonate or adult NSG mice and reconstituted the animals with human peripheral blood mononuclear cells (PBMCs). We also transplanted uninfected astrocytes into the brain of NSG mice and reconstituted with infected PBMCs to mimic a biological infection course. As expected, the xenotransplanted astrocytes did not escape/migrate out of the brai...Continue Reading

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Citations

Sep 22, 2020·Journal of Neuroinflammation· PriyankaPankaj Seth
Oct 22, 2020·MBio·Valérie LorinHugo Mouquet
Dec 3, 2020·The FEBS Journal·Murat SeyranBruce D Uhal
Nov 3, 2020·Frontiers in Cellular and Infection Microbiology·Caitlin TiceDianne Langford
Nov 12, 2020·Biomedicines·Venkata Viswanadh EdaraKathleen Borgmann
Feb 2, 2021·Neuroscience Letters·Melanie R Nicol, MaryPeace McRae
Apr 4, 2021·Biomolecules·Conlan KreherDaesung Shin
Apr 20, 2021·Frontiers in Cell and Developmental Biology·Supriya D MahajanJessica L Reynolds
Apr 13, 2021·The FEBS Journal·Avindra Nath, Tory P Johnson
Jun 3, 2021·International Journal of Environmental Research and Public Health·Rogers KaneeGaber El-Saber Batiha
Feb 4, 2022·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nabab KhanXuesong Chen

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Methods Mentioned

BETA
PCR
electrophoresis
flow
dot blots
flow cytometry
laser capture microdissection
transfection
density gradient centrifugation
dissection
confocal microscopy

Software Mentioned

PrimerQuest
GraphPad Prism
Geneious
Poisson
FlowJo
SDS2
Sequencher
Highlighter
NIS element
BD FACSDiva

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