Modeling Herpes Simplex Virus 1 Infections in Human Central Nervous System Neuronal Cells Using Two- and Three-Dimensional Cultures Derived from Induced Pluripotent Stem Cells

Journal of Virology
Leonardo D'AiutoVishwajit Nimgaonkar

Abstract

Herpes simplex virus 1 (HSV-1) establishes latency in both peripheral nerve ganglia and the central nervous system (CNS). The outcomes of acute and latent infections in these different anatomic sites appear to be distinct. It is becoming clear that many of the existing culture models using animal primary neurons to investigate HSV-1 infection of the CNS are limited and not ideal, and most do not recapitulate features of CNS neurons. Human induced pluripotent stem cells (hiPSCs) and neurons derived from them are documented as tools to study aspects of neuropathogenesis, but few have focused on modeling infections of the CNS. Here, we characterize functional two-dimensional (2D) CNS-like neuron cultures and three-dimensional (3D) brain organoids made from hiPSCs to model HSV-1-human-CNS interactions. Our results show that (i) hiPSC-derived CNS neurons are permissive for HSV-1 infection; (ii) a quiescent state exhibiting key landmarks of HSV-1 latency described in animal models can be established in hiPSC-derived CNS neurons; (iii) the complex laminar structure of the organoids can be efficiently infected with HSV, with virus being transported from the periphery to the central layers of the organoid; and (iv) the organoids support...Continue Reading

References

Sep 1, 1979·The Journal of General Virology·M S Ecob-Johnston, W O Whetsell
Dec 1, 1987·Journal of Virology·J G Spivack, N W Fraser
Oct 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·B WigdahlF Rapp
Jan 1, 1995·Progress in Nucleic Acid Research and Molecular Biology·E K WagnerJ Singh
Nov 5, 1997·Journal of Neurology, Neurosurgery, and Psychiatry·N McGrathK F Powell
Oct 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S RaoM F Shannon
Sep 19, 2003·The Journal of General Virology·Corinne PotelFlore Rozenberg
Jan 17, 2007·Genome Biology·Gwen LomberkRaul Urrutia
Jan 5, 2010·Biochimica Et Biophysica Acta·David C BloomDacia L Kwiatkowski
Aug 3, 2010·Neurobiology of Aging·Roberto PiacentiniClaudio Grassi
Jan 1, 2007·CSH Protocols·Marion CremerIrina Solovei
May 21, 2011·Brain Structure & Function·Lutz SlomiankaDavid P Wolfer
Jan 19, 2012·Pharmacology & Therapeutics·Anna AstashkinaDavid W Grainger
Feb 22, 2012·Frontiers in Microbiology·Jonathan Guito, David M Lukac
May 1, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joseph VithayathilGary E Landreth
Sep 5, 2015·Journal of Virology·Christine A KingSumita Bhaduri-McIntosh
Oct 27, 2015·Journal of Neurovirology·Lihong LiJumin Zhou
Jan 29, 2016·ACS Medicinal Chemistry Letters·James McNultyVishwajit L Nimgaonkar
Jun 12, 2016·Molecular Neurodegeneration·Claire S Harwell, Michael P Coleman
Nov 3, 2016·Frontiers in Aging Neuroscience·Giovanna De ChiaraDaniela Merlo
Mar 16, 2017·Development·Xuyu QianGuo-Li Ming
Mar 28, 2017·Antiviral Research·Leonardo D'AiutoVishwajit L Nimgaonkar

❮ Previous
Next ❯

Citations

Mar 29, 2020·Viruses·Vinod SundaramoorthyMegan Dearnley
Sep 17, 2020·Biotechnology Letters·Qiao Chen, Youbin Wang
Jun 5, 2020·Journal of Virology·Wenxiao ZhengLeonardo D'Aiuto
Oct 7, 2020·Brain : a Journal of Neurology·Polyxeni NikolakopoulouAnna Herland
Nov 27, 2020·Viruses·Adithya SridharKatja Wolthers
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Érika CossetKarl-Heinz Krause
Dec 4, 2020·Journal of Virology·Eric E AbrahamsonLeonardo D'Aiuto
Dec 31, 2020·Viruses·Christos DogrammatzisMaria Kalamvoki
Jul 9, 2020·Molecular Therapy. Methods & Clinical Development·Josse A DeplaMelvin M Evers
Feb 26, 2021·Stem Cell Reports·Anand RamaniJay Gopalakrishnan
Apr 4, 2021·International Journal of Molecular Sciences·Gianluca CostamagnaStefania Corti
May 5, 2021·Veterinary Research·Bertrand PainMuriel Coulpier
May 27, 2021·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Jing-Han NgEng-King Tan
Jul 13, 2021·Frontiers in Molecular Biosciences·Kseniia Sarieva, Simone Mayer
Aug 22, 2021·Drug Discovery Today·Anastasia ShpichkaPeter Timashev

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence microscopy
PCR
immunoprecipitation
ChIPs
ChIP
electrophoresis
Transmission electron microscopy
electron microscopy
chemical treatment
biopsy

Software Mentioned

AxoScope
Leica LAS AF
pClamp
GraphPad Prism

Related Concepts

Related Feeds

Brain Organoids in Disease Modeling

Brain organoids are three-dimensional cell culture models derived from human pluripotent stem cells. Since they resemble the embryonic brain, they can be used to help study brain biology, early brain development, and brain diseases. Discover the latest research on brain organoids in disease modeling here.

3D Cellular Models of Brain and Neurodegeneration

Brain organoids are three-dimensional in vitro cellular models of the brain that can recapitulate many processes such as the neurodevelopment. In addition, these organoids can be combined with other cell types, such as neurons and astrocytes to study their interactions in assembloids. Disease processes can also be modeled by induced pluripotent stem cell-derived organoids and assembloids from patients with neurodegenerative disorders. Discover the latest research on the models here.