Obesity Exacerbates Coxsackievirus Infection via Lipid-Induced Mitochondrial Reactive Oxygen Species Generation.
Seong-Ryeol KimJae-Hyoung SongJae-Hee AhnMyeong Seon JeongYoon Mee YangJaewon ChoJae-Hyeon JeongYounggil ChaKil-Nam KimHong Pyo KimSun-Young ChangHyun-Jeong KoPublished in: Immune network (2022)
Coxsackievirus B3 (CVB3) infection causes acute pancreatitis and myocarditis. However, its pathophysiological mechanism is unclear. Here, we investigated how lipid metabolism is associated with exacerbation of CVB3 pathology using high-fat diet (HFD)-induced obese mice. Mice were intraperitoneally inoculated with 1×10 6 pfu/mouse of CVB3 after being fed a control or HFD to induce obesity. Mice were treated with mitoquinone (MitoQ) to reduce the level of mitochondrial ROS (mtROS). In obese mice, lipotoxicity of white adipose tissue-induced inflammation caused increased replication of CVB3 and mortality. The coxsackievirus adenovirus receptor increased under obese conditions, facilitating CVB3 replication in vitro . However, lipid-treated cells with receptor-specific inhibitors did not reduce CVB3 replication. In addition, lipid treatment increased mitochondria-derived vesicle formation and the number of multivesicular bodies. Alternatively, we found that inhibition of lipid-induced mtROS decreased viral replication. Notably, HFD-fed mice were more susceptible to CVB3-induced mortality in association with increased levels of CVB3 replication in adipose tissue, which was ameliorated by administration of the mtROS inhibitor, MitoQ. These results suggest that mtROS inhibitors can be used as potential treatments for CVB3 infection.
Keyphrases
- high fat diet
- adipose tissue
- insulin resistance
- high glucose
- diabetic rats
- high fat diet induced
- oxidative stress
- reactive oxygen species
- metabolic syndrome
- type diabetes
- drug induced
- weight loss
- chronic obstructive pulmonary disease
- cell death
- intensive care unit
- induced apoptosis
- mass spectrometry
- sars cov
- physical activity
- combination therapy
- single molecule
- wild type
- stress induced