Human metapneumovirus inhibits IFN-β signaling by downregulating Jak1 and Tyk2 cellular levels

Junping Ren, Deepthi Kolli, Tianshuang Liu, Renling Xu, Roberto P. Garofalo, Antonella Casola, Xiaoyong Bao

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Article numbere24496
JournalPloS one
Volume6
Issue number9
DOIs
StatePublished - Sep 19 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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