Genetic and immunological contributors to virus-induced paralysis.
Brain Behav Immun Health
; 18: 100395, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34917987
ABSTRACT
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.
Amyotrophic Lateral Sclerosis, (ALS); Chromosome, (Chr); Chronic infection; Collaborative Cross, (CC); Collaborative cross; Cytokine; Epstein-Barr Virus, (EBV); Host response; IL-1 α; Multiple Sclerosis, (MS); Paralysis; Parkinson's disease, (PD); RANTES; TMEV; Theiler's murine encephalomyelitis virus, (TMEV); Viral infection; blood brain barrier, (BBB); central nervous system, (CNS); days post infection, (dpi); experimental autoimmune encephalitis, (EAE); intraperitoneal, (IP); phosphate buffered saline, (PBS); plaque-forming units, (PFU); receptor for IL-1 α, (Il1r1)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article