title: Coxsackievirus B3 induces the formation of autophagosomes in cardiac fibroblasts both in vitro and in vivo.
abstract: 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.
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: zhai_xia_cool@126.com.
authors: Xia
authors: X
authors: Zhai
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: qinyinggaofeng@163.com.
authors: Ying
authors: Y
authors: Qin
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: cy_hmu@126.com.
authors: Yang
authors: Y
authors: Chen
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: linlexun@163.com.
authors: Lexun
authors: L
authors: Lin
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: wangty0929@163.com.
authors: Tianying
authors: T
authors: Wang
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: littlerock712@163.com.
authors: Xiaoyan
authors: X
authors: Zhong
authors: Department of Cardiology, The First Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, China. Electronic address: xiaoyu_wu2006@163.com.
authors: Xiaoyu
authors: X
authors: Wu
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: chensj0802@163.com.
authors: Sijia
authors: S
authors: Chen
authors: Center of Electron Microscopy, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: jing070822@163.com.
authors: Jing
authors: J
authors: Li
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: wangyan@hrbmu.edu.cn.
authors: Yan
authors: Y
authors: Wang
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: fengminzhang@ems.hrbmu.edu.cn.
authors: Fengmin
authors: F
authors: Zhang
authors: Department of Cell Biology, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: zhaowenran2002@aliyun.com.
authors: Wenran
authors: W
authors: Zhao
authors: Department of Microbiology and Wu Lien-Teh Institute, Harbin Medical University, 157 Baojian Road, Harbin 150081, China. Electronic address: zhongzh@hrbmu.edu.cn.
authors: Zhaohua
authors: Z
authors: Zhong
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000821:virology*; D001343:Autophagy / Q000502:physiology; D029822:Enterovirus B, Human / Q000502:physiology; D005347:Fibroblasts / Q000821:virology*; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000821:virology*; D032383:Myocytes, Cardiac / Q000473:pathology / Q000821:virology*; D010588:Phagosomes / Q000821:virology; D014779:Virus Replication / Q000235:genetics
keywords: Autophagy; Cardiac fibroblast; Coxsackievirus B3; Pro-inflammatory cytokine