title: Recombinant lentivirus-delivered short hairpin RNAs targeted to conserved coxsackievirus sequences protect against viral myocarditis and improve survival rate in an animal model.
abstract: Coxsackieviruses are important human pathogens that induce myocarditis and pancreatitis. However, there are no vaccines or therapeutic reagents for their clinical treatment. Although RNA interference (RNAi)-based approaches to the prevention of viral production have been developed recently, limitations to the in vivo delivery systems and variations in the viral target sequences still hamper the strategy. In this study, to overcome these limitations, we have constructed recombinant lentivirus-delivered short hairpin RNAs (shRNAs) against sequences in highly conserved cis-acting replication element (CRE) within the 2C protein of coxsackievirus B3 (CVB3), designated MET-2C. A recombinant lentivirus, designated Met-2C lenti, was constructed that contains the MET-2C sequence, which acts as a shRNA. Met-2C lenti clearly reduced viral production in CVB3-infected cells in vitro. Moreover, the mice injected intraperitoneally with Met-2C lenti had significant reductions in viral titers, viral myocarditis, and proinflammatory cytokines after challenge with CVB3, compared with those in GFP lenti infected control mice. Moreover, Met-2C lenti improved survival rate compared with that of the GFP lenti infected control group. Therefore, Met-2C lenti is potentially a clinical therapeutic agent for the treatment of viral myocarditis.
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, 43-1, Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Korea.
authors.forename: Yeon-Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Jeonghyun
authors.initials: J
authors.lastname: Ahn
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Jeung
authors.forename: Dae-Sun
authors.initials: DS
authors.lastname: Kim
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Na
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Cho
authors.forename: Soo-Hyeon
authors.initials: SH
authors.lastname: Yun
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Jee
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Jeon
authors.forename: Heuiran
authors.initials: H
authors.lastname: Lee
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Nam
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003384:Coxsackievirus Infections / Q000276:immunology / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000517:prevention & control / Q000628:therapy* / Q000821:virology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D015850:Interleukin-6; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins; C076023:2C protein, viral