Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions

Virus-induced neurological sequelae resulting from infection by Theiler’s murine encephalomyelitis virus (TMEV) are used for studying human conditions ranging from epileptic seizures to demyelinating disease. Mouse strains are typically considered susceptible or resistant to TMEV infection based on...

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Autores principales:	Candice Brinkmeyer-Langford, Katia Amstalden, Kranti Konganti, Andrew Hillhouse, Koedi Lawley, Aracely Perez-Gomez, Colin R. Young, C. Jane Welsh, David W. Threadgill
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	TMEV resilience collaborative cross gene expression Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/b94d7cb237a74176a467cc326e4717c9
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spelling	oai:doaj.org-article:b94d7cb237a74176a467cc326e4717c92021-11-11T16:51:06ZResilience in Long-Term Viral Infection: Genetic Determinants and Interactions10.3390/ijms2221113791422-00671661-6596https://doaj.org/article/b94d7cb237a74176a467cc326e4717c92021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11379https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Virus-induced neurological sequelae resulting from infection by Theiler’s murine encephalomyelitis virus (TMEV) are used for studying human conditions ranging from epileptic seizures to demyelinating disease. Mouse strains are typically considered susceptible or resistant to TMEV infection based on viral persistence and extreme phenotypes, such as demyelination. We have identified a broader spectrum of phenotypic outcomes by infecting strains of the genetically diverse Collaborative Cross (CC) mouse resource. We evaluated the chronic-infection gene expression profiles of hippocampi and thoracic spinal cords for 19 CC strains in relation to phenotypic severity and TMEV persistence. Strains were clustered based on similar phenotypic profiles and TMEV levels at 90 days post-infection, and we categorized distinct TMEV response profiles. The three most common profiles included “resistant” and “susceptible,” as before, as well as a “resilient” TMEV response group which experienced both TMEV persistence and mild neurological phenotypes even at 90 days post-infection. Each profile had a distinct gene expression signature, allowing the identification of pathways and networks specific to each TMEV response group. CC founder haplotypes for genes involved in these pathways/networks revealed candidate response-specific alleles. These alleles demonstrated pleiotropy and epigenetic (miRNA) regulation in long-term TMEV infection, with particular relevance for resilient mouse strains.Candice Brinkmeyer-LangfordKatia AmstaldenKranti KongantiAndrew HillhouseKoedi LawleyAracely Perez-GomezColin R. YoungC. Jane WelshDavid W. ThreadgillMDPI AGarticleTMEVresiliencecollaborative crossgene expressionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11379, p 11379 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TMEV resilience collaborative cross gene expression Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	TMEV resilience collaborative cross gene expression Biology (General) QH301-705.5 Chemistry QD1-999 Candice Brinkmeyer-Langford Katia Amstalden Kranti Konganti Andrew Hillhouse Koedi Lawley Aracely Perez-Gomez Colin R. Young C. Jane Welsh David W. Threadgill Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions
description	Virus-induced neurological sequelae resulting from infection by Theiler’s murine encephalomyelitis virus (TMEV) are used for studying human conditions ranging from epileptic seizures to demyelinating disease. Mouse strains are typically considered susceptible or resistant to TMEV infection based on viral persistence and extreme phenotypes, such as demyelination. We have identified a broader spectrum of phenotypic outcomes by infecting strains of the genetically diverse Collaborative Cross (CC) mouse resource. We evaluated the chronic-infection gene expression profiles of hippocampi and thoracic spinal cords for 19 CC strains in relation to phenotypic severity and TMEV persistence. Strains were clustered based on similar phenotypic profiles and TMEV levels at 90 days post-infection, and we categorized distinct TMEV response profiles. The three most common profiles included “resistant” and “susceptible,” as before, as well as a “resilient” TMEV response group which experienced both TMEV persistence and mild neurological phenotypes even at 90 days post-infection. Each profile had a distinct gene expression signature, allowing the identification of pathways and networks specific to each TMEV response group. CC founder haplotypes for genes involved in these pathways/networks revealed candidate response-specific alleles. These alleles demonstrated pleiotropy and epigenetic (miRNA) regulation in long-term TMEV infection, with particular relevance for resilient mouse strains.
format	article
author	Candice Brinkmeyer-Langford Katia Amstalden Kranti Konganti Andrew Hillhouse Koedi Lawley Aracely Perez-Gomez Colin R. Young C. Jane Welsh David W. Threadgill
author_facet	Candice Brinkmeyer-Langford Katia Amstalden Kranti Konganti Andrew Hillhouse Koedi Lawley Aracely Perez-Gomez Colin R. Young C. Jane Welsh David W. Threadgill
author_sort	Candice Brinkmeyer-Langford
title	Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions
title_short	Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions
title_full	Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions
title_fullStr	Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions
title_full_unstemmed	Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions
title_sort	resilience in long-term viral infection: genetic determinants and interactions
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b94d7cb237a74176a467cc326e4717c9
work_keys_str_mv	AT candicebrinkmeyerlangford resilienceinlongtermviralinfectiongeneticdeterminantsandinteractions AT katiaamstalden resilienceinlongtermviralinfectiongeneticdeterminantsandinteractions AT krantikonganti resilienceinlongtermviralinfectiongeneticdeterminantsandinteractions AT andrewhillhouse resilienceinlongtermviralinfectiongeneticdeterminantsandinteractions AT koedilawley resilienceinlongtermviralinfectiongeneticdeterminantsandinteractions AT aracelyperezgomez resilienceinlongtermviralinfectiongeneticdeterminantsandinteractions AT colinryoung resilienceinlongtermviralinfectiongeneticdeterminantsandinteractions AT cjanewelsh resilienceinlongtermviralinfectiongeneticdeterminantsandinteractions AT davidwthreadgill resilienceinlongtermviralinfectiongeneticdeterminantsandinteractions
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Resilience in Long-Term Viral Infection: Genetic Determinants and Interactions

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