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Published on: June 14, 2020
The association between virus-induced spinal cord pathology and the genetic background of the host
Koedi S Lawley1, Tae Wook Kang1, Raquel R Rech2
1Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, United States.
Abstract:
Theiler's murine encephalomyelitis virus (TMEV) infection in mice has been used to study diverse neurological diseases, including multiple sclerosis and epilepsy. In this investigation, 5 strains of collaborative cross (CC) mice were infected with TMEV and examined clinically and histologically at days 4, 14, and 90 post-infection (dpi). All CC strains tested exhibited lumbar spinal cord and/or ventral peripheral nerve lesions by 14 dpi; CC027, CC023, and CC078 strains exhibited lesions at 4 dpi. At 90 dpi, lesions were remnants of the inflammatory responses associated with earlier infection; there was skeletal muscle atrophy in the CC023 strain. Increased microglial/macrophage reactivity was observed in all strains at 4 and 14 dpi, but not at 90 dpi. TMEV mRNA expression was greatest in the CC023 and CC078 strains at the acute timepoints; TMEV was completely cleared in all mice at 90 dpi. The neuropathological and clinical profiles in CC023 mice, mainly at 14 dpi, share some clinical and histologic features with those in amyotrophic lateral sclerosis patients. This work demonstrates how viral infection might interact with the genetic background of a susceptible individual to contribute to the onset, clinical presentation and persistence of lesions despite viral clearance.
Insights
Theiler's murine encephalomyelitis virus (TMEV) infection causes neurological lesions in susceptible mice, with genetic background influencing disease severity and persistence. Viral clearance occurs by 90 days post-infection, though residual inflammation and atrophy may persist.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) is a model for studying neurological diseases like multiple sclerosis and epilepsy.
- Collaborative cross (CC) mice offer a genetically diverse platform for investigating host-pathogen interactions.
Purpose of the Study:
- To investigate the neuropathological and clinical outcomes of TMEV infection across different CC mouse strains.
- To determine the role of genetic background in TMEV-induced neurological lesions and inflammatory responses.
Main Methods:
- Five CC mouse strains were infected with TMEV.
- Mice were assessed clinically and histologically at 4, 14, and 90 days post-infection (dpi).
- TMEV mRNA expression and microglial/macrophage reactivity were analyzed.
Main Results:
- All CC strains developed spinal cord and/or peripheral nerve lesions by 14 dpi.
- CC023 mice showed skeletal muscle atrophy and neuropathological features resembling amyotrophic lateral sclerosis at 14 dpi.
- TMEV was cleared by 90 dpi in all strains, but inflammatory remnants persisted.
Conclusions:
- Host genetic background significantly influences the susceptibility and progression of TMEV-induced neurological disease.
- TMEV infection can trigger persistent neuropathological changes even after viral clearance, highlighting the interplay between viral factors and host genetics.
