title: Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels.
abstract: Human metapneumovirus (hMPV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN) signaling by an unidentified mechanism. In this study, we showed that infection of airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2 (Tyk2), due to enhanced proteosomal degradation and reduced gene transcription. In addition, hMPV infection also reduced the surface expression of type I IFN receptor (IFNAR). These inhibitory mechanisms are different from the ones employed by respiratory syncytial virus (RSV), which does not affect Jak1, Tyk2 or IFNAR expression, but degrades downstream signal transducer and activator of transcription proteins 2 (STAT2), although both viruses are pneumoviruses belonging to the Paramyxoviridae family. Our study identifies a novel mechanism by which hMPV inhibits STAT1 and 2 activation, ultimately leading to viral evasion of host IFN responses.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, Galveston, Texas, United States of America.
authors.forename: Junping
authors.initials: J
authors.lastname: Ren
authors.forename: Deepthi
authors.initials: D
authors.lastname: Kolli
authors.forename: Tianshuang
authors.initials: T
authors.lastname: Liu
authors.forename: Renling
authors.initials: R
authors.lastname: Xu
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Garofalo
authors.forename: Antonella
authors.initials: A
authors.lastname: Casola
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Bao
mesh_terms: D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism / Q000821:virology*; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism* / Q000494:pharmacology; D053613:Janus Kinase 1 / Q000378:metabolism*; D029121:Metapneumovirus / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D059748:Proteolysis; D053633:Receptor, Interferon alpha-beta / Q000378:metabolism; D050795:STAT2 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D053634:TYK2 Kinase / Q000378:metabolism*; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D021122:Protein Subunits; D050795:STAT2 Transcription Factor; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D053613:Janus Kinase 1; D053634:TYK2 Kinase; D046988:Proteasome Endopeptidase Complex