Coxsackievirus B3 induces the formation of autophagosomes in cardiac fibroblasts both in vitro and in vivo

Journal Article · Sat Dec 10 00:00:00 EST 2016 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2016.10.020· OSTI ID:22649793

Zhai, Xia ^[1]; Qin, Ying ^[1]; Chen, Yang ^[1]; Lin, Lexun ^[1]; Wang, Tianying ^[1]; Zhong, Xiaoyan ^[1]; Wu, Xiaoyu ^[2]; Chen, Sijia ^[1]; Li, Jing ^[3]; Wang, Yan ^[1]; Zhang, Fengmin ^[1]; Zhao, Wenran ^[4]; others, and

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1. Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China)
2. Department of Cardiology, The First Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001 (China)
3. Center of Electron Microscopy, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China)
4. Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China)

Coxsackievirus group B (CVB) is one of the common pathogens that cause myocarditis and cardiomyopathy. Evidence has shown that CVB replication in cardiomyocytes is responsible for the damage and loss of cardiac muscle and the dysfunction of the heart. However, it remains largely undefined how CVB would directly impact cardiac fibroblasts, the most abundant cells in human heart. In this study, cardiac fibroblasts were isolated from Balb/c mice and infected with CVB type 3 (CVB3). Increased double-membraned, autophagosome-like vesicles in the CVB3-infected cardiac fibroblasts were observed with electron microscope. Punctate distribution of LC3 and increased level of LC3-II were also detected in the infected cardiac fibroblasts. Furthermore, we observed that the expression of pro-inflammatory cytokines, IL-6 and TNF-α, was increased in the CVB3-infected cardiac fibroblasts, while suppressed autophagy by 3-MA and Atg7-siRNA inhibited cytokine expression. Consistent with the in vitro findings, increased formation of autophagosomes was observed in the cardiac fibroblasts of Balb/c mice infected with CVB3. In conclusion, our data demonstrated that cardiac fibroblasts respond to CVB3 infection with the formation of autophagosomes and the release of the pro-inflammatory cytokines. These results suggest that the autophagic response of cardiac fibroblasts may play a role in the pathogenesis of myocarditis caused by CVB3 infection. - Highlights: • CVB3 replication induced autophagosome assembly in primary cardiac fibroblasts. • Both IL-6 and TNF-α in cardiac fibroblasts infected by CVB3 were increased. • IL-6 and TNF-α were reduced in cardiac fibroblasts when autophagy was inhibited. • Autophagosome assembly in cardiac fibroblasts of CVB-infected mice was increased.

• OSTI ID: 22649793
• Journal Information: Experimental Cell Research, Vol. 349, Issue 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CHAIN REACTIONS
DAMAGE
ELECTRON MICROSCOPES
FIBROBLASTS
FLUORESCENCE
HEART
HUMAN POPULATIONS
IN VITRO
IN VIVO
INFLAMMATION
INTERFERON
MEMBRANES
MICE
MICROTUBULES
MITOCHONDRIA
MUSCLES
NECROSIS
NEOPLASMS
PATHOGENESIS
PATHOGENS
PHOSPHOTRANSFERASES
POLYMERASE CHAIN REACTION
POLYMERASES
RADIOPROTECTIVE SUBSTANCES
RECEPTORS