title: Hemoglobin subunit beta interacts with the capsid protein and antagonizes the growth of classical swine fever virus.
abstract: The capsid (C) protein of the Flaviviridae family members is involved in nucleocapsid formation and virion assembly. However, the influence of C protein-interacting partners on the outcome of pestivirus infections is poorly defined. In this study, hemoglobin subunit beta (HB) was identified as a C protein-binding protein by glutathione S-transferase pulldown and subsequent mass spectrometry analysis of PK-15 cells, which are permissive cells for classical swine fever virus (CSFV). Coimmunoprecipitation and confocal microscopy confirmed that HB interacts and colocalizes with the C protein in the cytoplasm. Silencing of HB with small interfering RNAs promoted CSFV growth and replication, whereas overexpression of HB suppressed CSFV replication and growth. Interestingly, HB was found to interact with retinoic acid-inducible gene I and increase its expression, resulting in increased production of type I interferon (IFN). However, HB was unable to suppress CSFV growth when the RIG-I pathway was blocked. Overall, our results suggest that cellular HB antagonizes CSFV growth and replication by triggering IFN signaling, and might represent a novel antiviral restriction factor. This study reports for the first time the novel role of HB in innate immunity.
authors.affiliation: State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Dong
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.forename: Muhammad
authors.initials: M
authors.lastname: Munir
authors.forename: Jianing
authors.initials: J
authors.lastname: Chen
authors.forename: Yuzi
authors.initials: Y
authors.lastname: Luo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Lihong
authors.initials: L
authors.lastname: Liu
authors.forename: Hua-Ji
authors.initials: HJ
authors.lastname: Qiu
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism*; D002460:Cell Line; D002498:Centrifugation; D006692:Classical Swine Fever Virus / Q000472:pathogenicity* / Q000502:physiology; D018067:Flaviviridae; D006454:Hemoglobins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D018613:Microscopy, Confocal; D010576:Pestivirus; D011485:Protein Binding; D025941:Protein Interaction Mapping; D021122:Protein Subunits / Q000378:metabolism; D013552:Swine; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D036022:Capsid Proteins; D006454:Hemoglobins; D021122:Protein Subunits