Protein kinase B2 (PKB2/AKT2) is essential for host protection in CVB3-induced acute viral myocarditis = 숙주로부터 CVB3 유발 급성 바이러스성 심근염을 보호하기 위해 필수적인 Protein Kinase B2 (PKB2/AKT2)

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Title
Protein kinase B2 (PKB2/AKT2) is essential for host protection in CVB3-induced acute viral myocarditis = 숙주로부터 CVB3 유발 급성 바이러스성 심근염을 보호하기 위해 필수적인 Protein Kinase B2 (PKB2/AKT2)
Author(s)
S H Kim; H H Shin; J H Kim; Jung-Ho Park; E S Jeon; B K Lim
Bibliographic Citation
International Journal of Molecular Sciences, vol. 23, no. 3, pp. 1489-1489
Publication Year
2022
Abstract
Protein kinase B2 (AKT2) is involved in various cardiomyocyte signaling processes, including those important for survival and metabolism. Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. The role of AKT2 in CVB3 infection is not yet well understood. We used a cardiac-specific AKT2 knockout (KO) mouse to determine the role of AKT2 in CVB3-mediated myocarditis. CVB3 was injected intraperitoneally into wild-type (WT) and KO mice. The mice’s survival rate was recorded: survival in KO mice was significantly decreased compared with WT mice (WT vs. KO: 73.3 vs. 27.1%). Myocardial damage and inflammation were significantly increased in the hearts of KO mice compared with those of WT mice. Moreover, from surface ECG, AKT2 KO mice showed a prolonged atria and ventricle conduction time (PR interval, WT vs. KO: 47.27 ± 1.17 vs. 64.79 ± 7.17 ms). AKT2 deletion induced severe myocarditis and cardiac dysfunction due to CVB3 infection. According to real-time PCR, the mRNA level of IL-1, IL-6, and TNF-α decreased significantly in KO mice compared with WT mice on Days 5 after infection. In addition, innate immune response antiviral effectors, Type I interferon (interferon-α and β), and p62, were dramatically suppressed in the heart of KO mice. In particular, the adult cardiac myocytes isolated from the heart showed high induction of TLR4 protein in KO mice in comparison with WT. AKT2 deletion suppressed the activation of Type I interferon and p62 transcription in CVB3 infection. In cardiac myocytes, AKT2 is a key signaling molecule for the heart from damage through the activation of innate immunity during acute myocarditis.
Keyword
Coxsackievirus B3Protein kinase B2Toll-like-receptor4MyocarditisInnate immunity
ISSN
1661-6596
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ijms23031489
Type
Article
Appears in Collections:
Division of Bio Technology Innovation > Bio-Evaluation Center > 1. Journal Articles
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