Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mouse

A mouse-adapted isolate of Japanese encephalitis virus (JEV), designated as JEV-S3, was generated by serially passaging the P20778 strain of the virus in 3- to 4-week-old C57BL/6 mice. Blood-brain barrier leakage was evident in JEV-S3-infected mice, in which viral antigens and RNA were consistently...

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Main Authors: Aarti Tripathi, Arup Banerjee, Sudhanshu Vrati
Format: Article
Language:English
Published: The Company of Biologists 2021-10-01
Series:Disease Models & Mechanisms
Subjects:
Online Access:http://dmm.biologists.org/content/14/10/dmm049176
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author Aarti Tripathi
Arup Banerjee
Sudhanshu Vrati
author_facet Aarti Tripathi
Arup Banerjee
Sudhanshu Vrati
author_sort Aarti Tripathi
collection DOAJ
description A mouse-adapted isolate of Japanese encephalitis virus (JEV), designated as JEV-S3, was generated by serially passaging the P20778 strain of the virus in 3- to 4-week-old C57BL/6 mice. Blood-brain barrier leakage was evident in JEV-S3-infected mice, in which viral antigens and RNA were consistently demonstrated in the brain, along with infiltration of activated immune cells, as evidenced by an increased CD45+CD11b+ cell population. Histopathology studies showed the presence of perivascular cuffing, haemorrhage and necrotic foci in the virus-infected brain, conforming to the pathological changes seen in the brain of JEV-infected patients. Mass spectrometry studies characterized the molecular events leading to brain inflammation in the infected mice. Notably, a significant induction of inflammatory cytokines, such as IFNγ, IL6, TNFα and TGFβ, was observed. Further, genome sequencing of the JEV-S3 isolate identified the mutations selected during the mouse passage of the virus. Overall, we present an in-depth characterization of a robust and reproducible mouse model of JEV infection. The JEV-S3 isolate will be a useful tool to screen antivirals and study virus pathogenesis in the adolescent mouse model.
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spelling doaj.art-827123c53f50481fa4bc80d53f8953d82022-12-21T21:28:23ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112021-10-01141010.1242/dmm.049176049176Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mouseAarti Tripathi0Arup Banerjee1Sudhanshu Vrati2 Infection and Immunology, Translational Health Science and Technology Institute, Faridabad 121001, India Infection and Immunology, Translational Health Science and Technology Institute, Faridabad 121001, India Laboratory of Virology, Regional Centre for Biotechnology, Faridabad 121001, India A mouse-adapted isolate of Japanese encephalitis virus (JEV), designated as JEV-S3, was generated by serially passaging the P20778 strain of the virus in 3- to 4-week-old C57BL/6 mice. Blood-brain barrier leakage was evident in JEV-S3-infected mice, in which viral antigens and RNA were consistently demonstrated in the brain, along with infiltration of activated immune cells, as evidenced by an increased CD45+CD11b+ cell population. Histopathology studies showed the presence of perivascular cuffing, haemorrhage and necrotic foci in the virus-infected brain, conforming to the pathological changes seen in the brain of JEV-infected patients. Mass spectrometry studies characterized the molecular events leading to brain inflammation in the infected mice. Notably, a significant induction of inflammatory cytokines, such as IFNγ, IL6, TNFα and TGFβ, was observed. Further, genome sequencing of the JEV-S3 isolate identified the mutations selected during the mouse passage of the virus. Overall, we present an in-depth characterization of a robust and reproducible mouse model of JEV infection. The JEV-S3 isolate will be a useful tool to screen antivirals and study virus pathogenesis in the adolescent mouse model.http://dmm.biologists.org/content/14/10/dmm049176c57bl/6jev mouse modelvirulenceproteome profile
spellingShingle Aarti Tripathi
Arup Banerjee
Sudhanshu Vrati
Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mouse
Disease Models & Mechanisms
c57bl/6
jev mouse model
virulence
proteome profile
title Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mouse
title_full Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mouse
title_fullStr Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mouse
title_full_unstemmed Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mouse
title_short Development and characterization of an animal model of Japanese encephalitis virus infection in adolescent C57BL/6 mouse
title_sort development and characterization of an animal model of japanese encephalitis virus infection in adolescent c57bl 6 mouse
topic c57bl/6
jev mouse model
virulence
proteome profile
url http://dmm.biologists.org/content/14/10/dmm049176
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