Zika (PRVABC59) Infection Is Associated with T cell Infiltration and Neurodegeneration in CNS of Immunocompetent Neonatal C57Bl/6 Mice

PLoS Pathogens
Mohanraj ManangeeswaranDaniela Verthelyi

Abstract

The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently developed infection models for ZIKV utilize mice defective in interferon responses. In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice. We show that while ZIKV infected IFNAR KO mice develop bilateral hind limb paralysis and die 5-6 days post-infection (dpi), immunocompetent B6 WT mice develop signs of neurological disease including unsteady gait, kinetic tremors, severe ataxia and seizures by 13 dpi that subside gradually over 2 weeks. Immunohistochemistry show viral antigen predominantly in cerebellum at the peak of the disease in both models. However, whereas IFNAR KO mice showed infiltration by neutrophils and macrophages and higher expression of IL-1, IL-6 and Cox2, B6 W...Continue Reading

References

May 1, 1976·American Journal of Obstetrics and Gynecology·M S Amstey, K Kobos
Jan 1, 1976·The Journal of General Virology·J H WayG S Platt
Jul 1, 1988·Journal of Virology·S LustigJ H Strauss
Jan 1, 1971·Archiv für die gesamte Virusforschung·T M BellH K Narang
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Sep 1, 1952·Transactions of the Royal Society of Tropical Medicine and Hygiene·G W A DICK
Dec 4, 2003·Journal of Virology·Yang WangArno Müllbacher
Mar 16, 2005·Journal of Virology·Miki Ida-HosonumaSatoshi Koike
Apr 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·João A Pedras-VasconcelosDaniela Verthelyi
Jun 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·João A Pedras-VasconcelosDaniela Verthelyi
Aug 6, 2008·Emerging Infectious Diseases·Robert S LanciottiMark R Duffy
Mar 23, 2011·Neuroepidemiology·James J SejvarOliver W Morgan
Mar 23, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Arshed NazmiAnirban Basu
Oct 14, 2011·Viruses·Persephone BorrowJuan Carlos de la Torre
Apr 16, 2013·Progress in Neurobiology·Bridgette D SempleLinda J Noble-Haeusslein
Dec 10, 2013·Journal of Molecular Biology·Angela M GreenEva Harris
Nov 2, 2014·Proceedings of the National Academy of Sciences of the United States of America·Kirsten A KulcsarDiane E Griffin
Jun 19, 2015·Journal of Virology·Rodolphe HamelDorothée Missé
Feb 27, 2016·F1000Research·Evandro R WinkelmannTian Wang
Mar 16, 2016·Molecular BioSystems·Michael KennWolfgang Schreiner
Mar 30, 2016·The American Journal of Tropical Medicine and Hygiene·Shannan L RossiScott C Weaver
Apr 12, 2016·Science·Patricia P GarcezStevens K Rehen
Apr 14, 2016·Cell Host & Microbe·Helen M LazearMichael S Diamond
Apr 14, 2016·The New England Journal of Medicine·Sonja A RasmussenLyle R Petersen
Apr 20, 2016·PLoS Neglected Tropical Diseases·Matthew T AliotaJorge E Osorio
May 6, 2016·PLoS Neglected Tropical Diseases·Stuart DowallRoger Hewson
May 24, 2016·Nature Reviews. Microbiology·Ursula Hofer
Jun 10, 2016·Nature·Fernanda R CugolaPatricia C B Beltrão-Braga
Jun 30, 2016·Lancet·Leonelo E Bautista, Ajay K Sethi
Jul 20, 2016·The New England Journal of Medicine·Indira U Mysorekar, Michael S Diamond
Sep 11, 2016·Cell Reports·Jonathan J MinerRajendra S Apte

Citations

Apr 20, 2017·Cell Reports·Andrew K HastingsAkiko Iwasaki
Feb 16, 2017·Emerging Microbes & Infections·Joseph DarbellayUladzimir Karniychuk
Apr 13, 2017·Virology Journal·Mukesh KumarVivek R Nerurkar
Feb 10, 2017·Cell Host & Microbe·Jonathan J Miner, Michael S Diamond
Oct 20, 2017·Human Molecular Genetics·Pinar MesciAlysson R Muotri
Sep 14, 2017·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Kyle KuszpitThomas M Bocan
Dec 22, 2017·The Journal of Infectious Diseases·Justin G Julander, Venkatraman Siddharthan
Dec 6, 2017·American Journal of Reproductive Immunology : AJRI·Jun LeiIrina Burd
Mar 2, 2018·American Journal of Reproductive Immunology : AJRI·Christopher M NovakIrina Burd
Nov 15, 2017·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Jinsheng Wen, Sujan Shresta
Nov 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Amy B RosenfeldRichard B Vallee
Aug 25, 2017·Journal of Virology·Huarong HuangFuping Zhang
Feb 3, 2017·Journal of Virology·Thomas E Morrison, Michael S Diamond
Nov 3, 2017·Immune Network·Keeton KrauseMukesh Kumar
Jun 25, 2017·Acta Neuropathologica Communications·Stephanie L CumberworthJulia M Edgar
Sep 25, 2019·Microorganisms·Eleonora CiminiChiara Agrati
Feb 14, 2020·Journal of Virology·Laura E MartínezVaithilingaraja Arumugaswami
Apr 27, 2017·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Shashank S PawitwarNazira El-Hage
Mar 16, 2018·Virologica Sinica·Shupeng Dong, Qiming Liang
Aug 12, 2018·BMC Infectious Diseases·Carlos A A BritoRafael F O Franca
Aug 31, 2018·Nature·Theodore C Pierson, Michael S Diamond
Aug 7, 2019·Cells·Ryan D Pardy, Martin J Richer
Sep 26, 2020·Frontiers in Immunology·Loulieta NazeraiAllan Randrup Thomsen
Jun 2, 2017·Genes & Development·Zhexing WenGuo-Li Ming
May 29, 2018·Emerging Microbes & Infections·Mohanraj ManangeeswaranDaniela Verthelyi
Feb 20, 2019·Viruses·Francine AzouzMukesh Kumar
Nov 20, 2019·Cells·Ashley E SaverAndrea S Bertke
Mar 6, 2020·Frontiers in Immunology·Mohanraj ManangeeswaranDaniela Verthelyi
Nov 22, 2017·Nature Microbiology·Kellie A JuradoAkiko Iwasaki
Jun 22, 2018·Scientific Reports·Justin G JulanderJohn D Morrey
Apr 12, 2019·Frontiers in Cellular Neuroscience·Christian AlfanoLaurent Nguyen
Oct 20, 2020·Frontiers in Immunology·Alexander OschwaldDaniel Erny
Dec 11, 2020·PLoS Pathogens·Derek D C IrelandDaniela Verthelyi
Feb 9, 2020·The American Journal of Pathology·Gustavo GarciaVaithilingaraja Arumugaswami
Apr 29, 2020·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·Wei PangYong-Tang Zheng

Related Concepts

Zika Virus Disease (Disorder)
Metazoa
Brain
Flow Cytometry
Immunofluorescence Assay
Immunocytochemistry
Mice, Inbred C57BL
Nerve Degeneration
Mouse, Swiss
Kinetic Polymerase Chain Reaction

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.

Ataxias (MDS)

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.

Ataxias

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on different types of ataxias here.

Ataxia

Ataxia is a neurological condition characterized by lack of voluntary coordination of muscle movements including loss of coordination, balance, and speech. Discover the latest research on ataxia here.