title: Cyclophilin A protects mice against infection by influenza A virus.
abstract: Our previous studies indicate that Cyclophilin A (CypA) impairs the replication of influenza A virus in vitro. To further evaluate the antiviral functions of CypA and explore its mechanism, transgenic mice with overexpression of CypA by two specific promoters with SPC (CypA-SPC) or CMV (CypA-CMV) were developed. After challenge with the A/WSN/33(H1N1) influenza virus, CypA-SPC and CypA-CMV transgenic mice displayed nearly 2.5- and 3.8-fold stronger disease resistance to virus infection, respectively, compared to wild-type animals. Virus replication, pathological lesions and inflammatory cytokines were substantially reduced in both lines of transgenic mice. In addition, after infection there was an upregulation of genes associated with cell migration, immune function, and organ development; and a downregulation of genes associated with the positive regulation of immune cells and apoptosis in the peritoneal macrophages of CypA-overexpressing transgenic mice (CypA+). These results indicate that CypA is a key modulator of influenza virus resistance in mice, and that CypA+ mice constitutes an important model to study the roles of CypA in the regulation of immune responses and infections.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Can
authors.initials: C
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Gary
authors.initials: G
authors.lastname: Wong
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, Beijing, 100021 China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dong
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Weinan
authors.initials: W
authors.lastname: Zheng
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.affiliation: Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences &Comparative Medical Center, Peking Union Medical College, Beijing, 100021 China.
authors.forename: Lianfeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Bi
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.|Center for Influenza Research and Early-warning (CASCIRE), Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D021984:Cyclophilin A / Q000235:genetics*; D060467:Disease Resistance; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D009980:Influenza A virus / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000517:prevention & control* / Q000662:veterinary; D011401:Promoter Regions, Genetic; D014779:Virus Replication
chemical_list: D021984:Cyclophilin A