Genetic and immunological contributors to virus-induced paralysis

Infection by a single virus can evoke diverse immune responses, resulting in different neurological outcomes, depending on the host's genetic background. To study heterogenous viral response, we use Theiler's Murine Encephalomyelitis Virus (TMEV) to model virally induced neurological pheno...

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Autores principales:	Aracely A. Perez Gomez, Moumita Karmakar, Raymond J. Carroll, Koedi S. Lawley, Katia Amstalden, Colin R. Young, David W. Threadgill, C. Jane Welsh, Candice Brinkmeyer-Langford
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Chronic infection Collaborative cross Cytokine Host response IL-1 α Paralysis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/41686c51fd94412ab8c544806cc8050e
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spelling	oai:doaj.org-article:41686c51fd94412ab8c544806cc8050e2021-12-02T05:03:43ZGenetic and immunological contributors to virus-induced paralysis2666-354610.1016/j.bbih.2021.100395https://doaj.org/article/41686c51fd94412ab8c544806cc8050e2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666354621001988https://doaj.org/toc/2666-3546Infection by a single virus can evoke diverse immune responses, resulting in different neurological outcomes, depending on the host's genetic background. To study heterogenous viral response, we use Theiler's Murine Encephalomyelitis Virus (TMEV) to model virally induced neurological phenotypes and immune responses in Collaborative Cross (CC) mice. The CC resource consists of genetically distinct and reproducible mouse lines, thus providing a population model with genetic heterogeneity similar to humans. We examined different CC strains for the effect of chronic stage TMEV-induced immune responses on neurological outcomes throughout 90 days post infection (dpi), with a particular focus on limb paralysis, by measuring serum levels of 23 different cytokines and chemokines. Each CC strain demonstrated a unique set of immune responses, regardless of presence or absence of TMEV RNA. Using stepwise regression, significant associations were identified between IL-1α, RANTES, and paralysis frequency scores. To better understand these interactions, we evaluated multiple aspects of the different CC genetic backgrounds, including haplotypes of genomic regions previously linked with TMEV pathogenesis and viral clearance or persistence, individual cytokine levels, and TMEV-relevant gene expression. These results demonstrate how loci previously associated with TMEV outcomes provide incomplete information regarding TMEV-induced paralysis in the CC strains. Overall, these findings provide insight into the complex roles of immune response in the pathogenesis of virus-associated neurological diseases influenced by host genetic background.Aracely A. Perez GomezMoumita KarmakarRaymond J. CarrollKoedi S. LawleyKatia AmstaldenColin R. YoungDavid W. ThreadgillC. Jane WelshCandice Brinkmeyer-LangfordElsevierarticleChronic infectionCollaborative crossCytokineHost responseIL-1 αParalysisNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENBrain, Behavior, & Immunity - Health, Vol 18, Iss , Pp 100395- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chronic infection Collaborative cross Cytokine Host response IL-1 α Paralysis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Chronic infection Collaborative cross Cytokine Host response IL-1 α Paralysis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Aracely A. Perez Gomez Moumita Karmakar Raymond J. Carroll Koedi S. Lawley Katia Amstalden Colin R. Young David W. Threadgill C. Jane Welsh Candice Brinkmeyer-Langford Genetic and immunological contributors to virus-induced paralysis
description	Infection by a single virus can evoke diverse immune responses, resulting in different neurological outcomes, depending on the host's genetic background. To study heterogenous viral response, we use Theiler's Murine Encephalomyelitis Virus (TMEV) to model virally induced neurological phenotypes and immune responses in Collaborative Cross (CC) mice. The CC resource consists of genetically distinct and reproducible mouse lines, thus providing a population model with genetic heterogeneity similar to humans. We examined different CC strains for the effect of chronic stage TMEV-induced immune responses on neurological outcomes throughout 90 days post infection (dpi), with a particular focus on limb paralysis, by measuring serum levels of 23 different cytokines and chemokines. Each CC strain demonstrated a unique set of immune responses, regardless of presence or absence of TMEV RNA. Using stepwise regression, significant associations were identified between IL-1α, RANTES, and paralysis frequency scores. To better understand these interactions, we evaluated multiple aspects of the different CC genetic backgrounds, including haplotypes of genomic regions previously linked with TMEV pathogenesis and viral clearance or persistence, individual cytokine levels, and TMEV-relevant gene expression. These results demonstrate how loci previously associated with TMEV outcomes provide incomplete information regarding TMEV-induced paralysis in the CC strains. Overall, these findings provide insight into the complex roles of immune response in the pathogenesis of virus-associated neurological diseases influenced by host genetic background.
format	article
author	Aracely A. Perez Gomez Moumita Karmakar Raymond J. Carroll Koedi S. Lawley Katia Amstalden Colin R. Young David W. Threadgill C. Jane Welsh Candice Brinkmeyer-Langford
author_facet	Aracely A. Perez Gomez Moumita Karmakar Raymond J. Carroll Koedi S. Lawley Katia Amstalden Colin R. Young David W. Threadgill C. Jane Welsh Candice Brinkmeyer-Langford
author_sort	Aracely A. Perez Gomez
title	Genetic and immunological contributors to virus-induced paralysis
title_short	Genetic and immunological contributors to virus-induced paralysis
title_full	Genetic and immunological contributors to virus-induced paralysis
title_fullStr	Genetic and immunological contributors to virus-induced paralysis
title_full_unstemmed	Genetic and immunological contributors to virus-induced paralysis
title_sort	genetic and immunological contributors to virus-induced paralysis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/41686c51fd94412ab8c544806cc8050e
work_keys_str_mv	AT aracelyaperezgomez geneticandimmunologicalcontributorstovirusinducedparalysis AT moumitakarmakar geneticandimmunologicalcontributorstovirusinducedparalysis AT raymondjcarroll geneticandimmunologicalcontributorstovirusinducedparalysis AT koedislawley geneticandimmunologicalcontributorstovirusinducedparalysis AT katiaamstalden geneticandimmunologicalcontributorstovirusinducedparalysis AT colinryoung geneticandimmunologicalcontributorstovirusinducedparalysis AT davidwthreadgill geneticandimmunologicalcontributorstovirusinducedparalysis AT cjanewelsh geneticandimmunologicalcontributorstovirusinducedparalysis AT candicebrinkmeyerlangford geneticandimmunologicalcontributorstovirusinducedparalysis
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Genetic and immunological contributors to virus-induced paralysis

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