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

International Journal of Molecular Sciences

Katia Amstalden¹  Candice Brinkmeyer-Langford¹  Colin R. Young¹  C. Jane Welsh¹  Aracely Perez-Gomez¹  Koedi Lawley¹  David W. Threadgill²  Kranti Konganti²  Andrew Hillhouse² 

[1] Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA;Texas A&M Institute for Genome Sciences and Society, Texas A&M University, College Station, TX 77843, USA;

关键词: TMEV;    resilience;    collaborative cross;    gene expression;   

DOI  :  10.3390/ijms222111379

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown