title: Umifenovir effectively inhibits IL-10 dependent persistent Coxsackie B4 virus infection.
abstract: Coxsackie virus cannot be completely eliminated due to restrictive replication and impaired immune response, thus causing persistent infection. IL-10 plays a decisive role in the course of persistent viral infection. Umifenovir is a broad-spectrum antiviral drug, with certain treatment effects on Coxsackie virus infection. Previously, we showed that in addition to inhibiting Coxsackie B4 (CVB4) infection, Umifenovir also down-regulates IL-10 induced by persistent CVB4 virus infection in vitro and in vivo. Here, BALB/c mouse spleen cells infected with CVB4 were used as a model to explore the mechanism by which Umifenovir affects IL-10 expression. We found that subcellular localization of p38 and MAPK-activated protein kinase 2 (MK2) played a very important role in IL-10 secretion, and Umifenovir significantly prevented p38-MK2 complex from exiting the cell nucleus. This in turn blocked the biological functions of the latter pathway, and inhibited the high expression of IL-10 induced by CVB4. These findings suggest that Umifenovir is a potential anti-CVB4 drug; most importantly, Umifenovir could be used to treat IL-10 induced persistent viral infection.
authors.affiliation: Cancer Center, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, People's Republic of China.
authors.forename: Shilin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Anus Bowel Division, Affiliated Hospital of Changchun University of Chinese Medicine, 1478 Gongnong Road, Changchun, 130021, People's Republic of China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Zhi
authors.affiliation: Institute of Frontier Medical Science of Jilin University, 1163 Xinmin Street, Changchun, 130021, People's Republic of China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Frontier Medical Science of Jilin University, 1163 Xinmin Street, Changchun, 130021, People's Republic of China.
authors.forename: Dianshuai
authors.initials: D
authors.lastname: Huang
authors.affiliation: Institute of Frontier Medical Science of Jilin University, 1163 Xinmin Street, Changchun, 130021, People's Republic of China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Cancer Center, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, People's Republic of China. Electronic address: cuijw@jlu.edu.cn.
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Cui
authors.affiliation: Institute of Frontier Medical Science of Jilin University, 1163 Xinmin Street, Changchun, 130021, People's Republic of China. Electronic address: liang@jlu.edu.cn.
authors.forename: Chongyang
authors.initials: C
authors.lastname: Liang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000821:virology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D056747:Immunomodulation; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009205:Myocarditis / Q000188:drug therapy / Q000821:virology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000821:virology; D048051:p38 Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2; D013440:Sulfides
chemical_list: D000998:Antiviral Agents; D007211:Indoles; D016753:Interleukin-10; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C086979:umifenovir; D013440:Sulfides
keywords: Coxsackie B4; IL-10; MAPK-activated protein kinase 2; P38 MAPK; Umifenovir; Viral myocarditis