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Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology

Differences in disease outcome between the highly neurovirulent MHV-JHM and mildly neurovirulent MHV-A59 have been attributed to variations within the spike (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by diminished expression of interferon-γ (IFN-γ) mRNA and a reduc...

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Autores principales: Rempel, Julia D., Murray, Shannon J., Meisner, Jeffrey, Buchmeier, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126387/
https://www.ncbi.nlm.nih.gov/pubmed/14972534
http://dx.doi.org/10.1016/j.virol.2003.08.041
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author Rempel, Julia D.
Murray, Shannon J.
Meisner, Jeffrey
Buchmeier, Michael J.
author_facet Rempel, Julia D.
Murray, Shannon J.
Meisner, Jeffrey
Buchmeier, Michael J.
author_sort Rempel, Julia D.
collection PubMed
description Differences in disease outcome between the highly neurovirulent MHV-JHM and mildly neurovirulent MHV-A59 have been attributed to variations within the spike (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by diminished expression of interferon-γ (IFN-γ) mRNA and a reduced presence of CD8 T cells in the CNS concomitant with heightened macrophage inflammatory protein (MIP)-1 transcript levels and greater macrophage infiltration relative to MHV-A59 infection. Here, the ability of the S and non-spike genes to regulate these immune responses was evaluated using chimeric viruses. Chimeric viruses WTR13 and S4R22 were made on MHV-A59 variant backgrounds and, respectively, contained the S gene of MHV-A59 and MHV-JHM. Unexpectedly, genes other than S appeared to modulate events critical to viral replication and survival. Unlike unresolving MHV-JHM infections, the clearance of WTR13 and S4R22 infections coincided with strong IFN-γ transcription and an increase in the number of CD8 T cells infiltrating into the CNS. However, despite the absence of detectable viral titers, approximately 40% of S4R22-infected mice succumbed within 3 weeks, indicating that the enhanced mortality following S4R22 infection was not associated with high viral titers. Instead, similar to the MHV-JHM infection, reduced survival following S4R22 infection was observed in the presence of elevated MIP-1α and MIP-1β mRNA accumulation and enhanced macrophage numbers within infected brains. These observations suggest that the S protein of MHV-JHM influences neurovirulence through the induction of MIP-1α- and MIP-1β-driven macrophage immunopathology.
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spelling pubmed-71263872020-04-08 Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology Rempel, Julia D. Murray, Shannon J. Meisner, Jeffrey Buchmeier, Michael J. Virology Article Differences in disease outcome between the highly neurovirulent MHV-JHM and mildly neurovirulent MHV-A59 have been attributed to variations within the spike (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by diminished expression of interferon-γ (IFN-γ) mRNA and a reduced presence of CD8 T cells in the CNS concomitant with heightened macrophage inflammatory protein (MIP)-1 transcript levels and greater macrophage infiltration relative to MHV-A59 infection. Here, the ability of the S and non-spike genes to regulate these immune responses was evaluated using chimeric viruses. Chimeric viruses WTR13 and S4R22 were made on MHV-A59 variant backgrounds and, respectively, contained the S gene of MHV-A59 and MHV-JHM. Unexpectedly, genes other than S appeared to modulate events critical to viral replication and survival. Unlike unresolving MHV-JHM infections, the clearance of WTR13 and S4R22 infections coincided with strong IFN-γ transcription and an increase in the number of CD8 T cells infiltrating into the CNS. However, despite the absence of detectable viral titers, approximately 40% of S4R22-infected mice succumbed within 3 weeks, indicating that the enhanced mortality following S4R22 infection was not associated with high viral titers. Instead, similar to the MHV-JHM infection, reduced survival following S4R22 infection was observed in the presence of elevated MIP-1α and MIP-1β mRNA accumulation and enhanced macrophage numbers within infected brains. These observations suggest that the S protein of MHV-JHM influences neurovirulence through the induction of MIP-1α- and MIP-1β-driven macrophage immunopathology. Elsevier Inc. 2004-01-05 2004-01-07 /pmc/articles/PMC7126387/ /pubmed/14972534 http://dx.doi.org/10.1016/j.virol.2003.08.041 Text en Copyright © 2003 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Rempel, Julia D.
Murray, Shannon J.
Meisner, Jeffrey
Buchmeier, Michael J.
Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology
title Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology
title_full Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology
title_fullStr Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology
title_full_unstemmed Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology
title_short Mouse hepatitis virus neurovirulence: evidence of a linkage between S glycoprotein expression and immunopathology
title_sort mouse hepatitis virus neurovirulence: evidence of a linkage between s glycoprotein expression and immunopathology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7126387/
https://www.ncbi.nlm.nih.gov/pubmed/14972534
http://dx.doi.org/10.1016/j.virol.2003.08.041
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