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

Authors :
Andrew Hillhouse
C. Jane Welsh
Aracely Perez-Gomez
David W. Threadgill
Koedi S. Lawley
Colin R. Young
Candice Brinkmeyer-Langford
Katia Amstalden
Kranti Konganti
Source :
International Journal of Molecular Sciences, Volume 22, Issue 21, International Journal of Molecular Sciences, Vol 22, Iss 11379, p 11379 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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.

Details

ISSN :
14220067
Volume :
22
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences
Accession number :
edsair.doi.dedup.....46ddd59a478a70a0533ad51860e1fcf9