title: Transcriptome profiling indicating canine parvovirus type 2a as a potential immune activator.
abstract: Canine parvovirus type 2a (CPV-2a) is a variant of CPV-2, which is a highly contagious pathogen causing severe gastroenteritis and death in young dogs. However, how CPV-2 participates in cell regulation and immune response remains unknown. In this study, persistently infected MDCK cells were generated through culture passage of the CPV-2a-infected cells for ten generations. Our study showed that CPV-2a induces cell proliferation arrest and cell morphology alternation before the fourth generation, whereas, the cell morphology returns to normal after five times of passages. PCR detection of viral VP2 gene demonstrated that CPV-2a proliferate with cell passage. An immunofluorescence assay revealed that CPV-2a particles were mainly located in the cell nuclei of MDCK cell. Then transcriptome microarray revealed that gene expression pattern of MDCK with CPV-2a persistent infection is distinct compared with normal cells. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genome pathway analysis demonstrated that CPV-2a infection induces a series of membrane-associated genes expression, including many MHC protein or MHC-related complexes. These genes are closely related to signaling pathways of virus-host interaction, including antigen processing and presentation pathway, intestinal immune network, graft-versus-host disease, and RIG-I-like helicases signaling pathway. In contrast, the suppressed genes mediated by CPV-2a showed low enrichment in any category, and were only involved in pathways linking to synthesis and metabolism of amino acids, which was confirmed by qPCR analysis. Our studies indicated that CPV-2a is a natural immune activator and has the capacity to activate host immune responses, which could be used for the development of antiviral strategy and biomaterial for medicine.
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, 730046, Gansu, China.
authors.forename: Xu-Xu
authors.initials: XX
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, 730046, Gansu, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, 730046, Gansu, China.|College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
authors.forename: Long
authors.initials: L
authors.lastname: Shu
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, 730046, Gansu, China.
authors.forename: Yan-Quan
authors.initials: YQ
authors.lastname: Wei
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Yao
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China. 736570504@qq.com.
authors.forename: Sui-Zhong
authors.initials: SZ
authors.lastname: Cao
authors.affiliation: College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
authors.forename: Guang-Neng
authors.initials: GN
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, 730046, Gansu, China.
authors.forename: Xiang-Tao
authors.initials: XT
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, 730046, Gansu, China. sunshiqi@caas.cn.
authors.forename: Shi-Qi
authors.initials: SQ
authors.lastname: Sun
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016000:Cluster Analysis; D019295:Computational Biology; D004285:Dogs; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000276:immunology*; D056747:Immunomodulation; D058977:Molecular Sequence Annotation; D010322:Parvoviridae Infections / Q000276:immunology / Q000821:virology; D017993:Parvovirus, Canine / Q000235:genetics* / Q000276:immunology*; D015203:Reproducibility of Results; D015398:Signal Transduction; D059467:Transcriptome
keywords: CPV-2a; Immune activator; MDCK; Persistent infection