Version 1
: Received: 20 June 2024 / Approved: 21 June 2024 / Online: 21 June 2024 (08:10:56 CEST)
How to cite:
Oliveira Lopes da Silva, M.; Menezes Figueiredo, C.; Leão da Silva Neris, R.; Guimarães-Andrade, I. P.; Gavino-Leopoldino, D.; Linhares Miler-da-Silva, L.; da Maia Valença, H.; Ladislau, L.; Victorino Felix de Lima, C.; Meireles Coccarelli, F.; Farias Benjamim, C.; Miranda, I. Chikungunya and Mayaro Viruses Induce Chronic Skeletal Muscle Atrophy Triggered by Pro-inflammatory and Oxidative Response. Preprints2024, 2024061490. https://doi.org/10.20944/preprints202406.1490.v1
Oliveira Lopes da Silva, M.; Menezes Figueiredo, C.; Leão da Silva Neris, R.; Guimarães-Andrade, I. P.; Gavino-Leopoldino, D.; Linhares Miler-da-Silva, L.; da Maia Valença, H.; Ladislau, L.; Victorino Felix de Lima, C.; Meireles Coccarelli, F.; Farias Benjamim, C.; Miranda, I. Chikungunya and Mayaro Viruses Induce Chronic Skeletal Muscle Atrophy Triggered by Pro-inflammatory and Oxidative Response. Preprints 2024, 2024061490. https://doi.org/10.20944/preprints202406.1490.v1
Oliveira Lopes da Silva, M.; Menezes Figueiredo, C.; Leão da Silva Neris, R.; Guimarães-Andrade, I. P.; Gavino-Leopoldino, D.; Linhares Miler-da-Silva, L.; da Maia Valença, H.; Ladislau, L.; Victorino Felix de Lima, C.; Meireles Coccarelli, F.; Farias Benjamim, C.; Miranda, I. Chikungunya and Mayaro Viruses Induce Chronic Skeletal Muscle Atrophy Triggered by Pro-inflammatory and Oxidative Response. Preprints2024, 2024061490. https://doi.org/10.20944/preprints202406.1490.v1
APA Style
Oliveira Lopes da Silva, M., Menezes Figueiredo, C., Leão da Silva Neris, R., Guimarães-Andrade, I. P., Gavino-Leopoldino, D., Linhares Miler-da-Silva, L., da Maia Valença, H., Ladislau, L., Victorino Felix de Lima, C., Meireles Coccarelli, F., Farias Benjamim, C., & Miranda, I. (2024). Chikungunya and Mayaro Viruses Induce Chronic Skeletal Muscle Atrophy Triggered by Pro-inflammatory and Oxidative Response. Preprints. https://doi.org/10.20944/preprints202406.1490.v1
Chicago/Turabian Style
Oliveira Lopes da Silva, M., Claudia Farias Benjamim and Iranaia Miranda. 2024 "Chikungunya and Mayaro Viruses Induce Chronic Skeletal Muscle Atrophy Triggered by Pro-inflammatory and Oxidative Response" Preprints. https://doi.org/10.20944/preprints202406.1490.v1
Abstract
Chikungunya (CHIKV) and Mayaro (MAYV) viruses are arthritogenic alphaviruses that promote an incapacitating and long-lasting inflammatory muscle-articular disease. Despite studies pointing out the importance of skeletal muscle (SkM) in viral pathogenesis, the long-term consequences on its physiology after acute injury and the mechanism of persistence of symptoms are still poorly understood. Combining molecular, morphological, Nuclear Magnetic Resonance Imaging, and histological analysis, we conduct a temporal investigation of CHIKV and MAYV replication in a wild-type mice model, focusing on the impact on SkM composition, structure, and repair in the acute and late phases of infection. We found that viral replication and induced-inflammation promote fast loss of muscle mass and reduction of fibers cross sectional area, by inducing muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin expression, that trigger protein breakdown, resulting in acute SkM fibers atrophy. After temporal reduction of inflammation and clearance of infectious viral particles, SkM atrophy persists until the late phase of infection. The genomic CHIKV and MAYV RNAs were still detected in SkM at the late phase, along with increased levels of chemokines and anti-inflammatory cytokines expression. In agreement with the involvement of inflammatory mediators on induced atrophy, neutralization of TNF and the reduction of oxidative stress using monomethyl fumarate, an agonist of Nrf2, decreases atrogens expression and atrophic fibers, while increasing weight gain in treated mice. Taken together, these data indicate that arthritogenic alphavirus infection could chronically impact body SkM composition and also harm repair machinery, contributing to a better understanding of mechanisms of arthritogenic alphaviruses pathogenesis and with description of potentially new targets of therapeutic intervention.
Keywords
Arthritogenic alphavirus; skeletal muscle; chronic atrophy; inflammation and oxidative stress
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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