title: Cyclophilin A inhibits rotavirus replication by facilitating host IFN-I production.
abstract: Rotavirus (RV) infection causes serious dehydrating diarrhoea in infants and newborn animals. Our previous study revealed that cyclophilin A (CYPA), a peptidyl-prolyl cis-trans isomerase (PPIase), could be temporarily upregulated in RV-infected MA104 cells in early stage of infection (unpublished data). To find out the possible roles of CYPA in RV infection, we overexpressed and silenced CYPA in various cell lines by gene transfection and shRNA. We found that transfection of CYPA significantly inhibited RV replication, while silencing the expression of CYPA significantly increased RV replication. Accordingly, overexpression of CYPA significantly increased IFN-β production; while silencing CYPA significantly reduced IFN-β production. This effect of CYPA on IFN-β production was independent of its PPIase activity. Moreover, IFN-β secreted by host cells in RV infection had a critical repressive effect on viral replication. Finally, we found that inhibiting JNK pathway by SP600125 and JNK siRNA abrogated the effect of CYPA on IFN-β transcription in RV-infected MA104 cells. Together, our data suggested that CYPA inhibited RV replication by facilitating host IFN-β production, which was independent on the PPIase activity of CYPA but dependent on the activation of JNK signaling pathway.
authors.affiliation: Institute of Immunology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: He
authors.forename: Daijun
authors.initials: D
authors.lastname: Zhou
authors.forename: Weiping
authors.initials: W
authors.lastname: Fan
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Fu
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Zigang
authors.initials: Z
authors.lastname: Shen
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Jintao
authors.initials: J
authors.lastname: Li
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002460:Cell Line; D021984:Cyclophilin A / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D012401:Rotavirus / Q000502:physiology*; D012400:Rotavirus Infections / Q000378:metabolism* / Q000821:virology; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D016899:Interferon-beta; D048670:MAP Kinase Kinase 4; D021984:Cyclophilin A