title: Gene expression analysis during recovery process indicates the mechanism for innate immune injury and repair from Coxsackievirus B3-induced myocarditis.
abstract: To investigate the innate immune injury and repair mechanism during recovery from Coxsackievirus B3 (CVB3) induced myocarditis, we established an acute viral myocarditis recovery model by infecting BALB/c mice with CVB3. Histopathological examination of cardiac tissues after infection showed a gradual increase of myocardial injury to the maximum degree at 8 dpi (days post infection), followed by a recovery process with reduced viral replication. We also measured expression changes of innate immune genes in heart after 4, 8 and 12 days of infection using innate immune real-time PCR array. The results showed expression alterations in many Pattern Recognition Receptors (PRRs) genes upon CVB3 infection, which activated multiple important signaling pathways during recovery process. The expression of TLRs, RLRs, PKR and cytokines were strongly induced and reached the peak at 4 dpi in early myocarditis stage, followed by a gradual reduction in recovery stage, during which the levels were even lower than normal at 12 dpi. The strong correlation between cardiac histopathology score and chemokine expression level suggested that the chemokines might play a role in pathological changes during early myocarditis stage. In addition, we also found that both cell survival signaling pathways (AKT1, p38MAPK) and antiviral signaling pathways (IKKα/β/ε) were activated and promoted the recovery during late myocarditis stage. Altogether, our observations improved the understanding of formation and progression of the pathological lesions, as well as the repair mechanism for acute viral myocarditis.
authors.affiliation: Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China; Molecular Immunology Laboratory, Capital Institute of Pediatrics, 2 YaBao Road, Beijing 100020, China.
authors.forename: Hai-Lan
authors.initials: HL
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.affiliation: Inner Mongolia Medical University, Hollyhock 010110, Jingshang Development Zone, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, China.
authors.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Song
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, China.
authors.forename: Lin-Jun
authors.initials: LJ
authors.lastname: Sheng
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, China.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Chi
authors.affiliation: State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, China. Electronic address: hanjun_sci@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000254:growth & development* / Q000276:immunology*; D020869:Gene Expression Profiling; D006651:Histocytochemistry; D007113:Immunity, Innate; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D009206:Myocardium / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018925:Chemokines
keywords: Chemokine; Coxsackievirus B3; Innate immune; Interferon; PRRs; Viral myocarditis