title: Unique nonstructural proteins of Pneumonia Virus of Mice (PVM) promote degradation of interferon (IFN) pathway components and IFN-stimulated gene proteins.
abstract: Pneumonia Virus of Mice (PVM) is the only virus that shares the Pneumovirus genus of the Paramyxoviridae family with Respiratory Syncytial Virus (RSV). A deadly mouse pathogen, PVM has the potential to serve as a robust animal model of RSV infection, since human RSV does not fully replicate the human pathology in mice. Like RSV, PVM also encodes two nonstructural proteins that have been implicated to suppress the IFN pathway, but surprisingly, they exhibit no sequence similarity with their RSV equivalents. The molecular mechanism of PVM NS function, therefore, remains unknown. Here, we show that recombinant PVM NS proteins degrade the mouse counterparts of the IFN pathway components. Proteasomal degradation appears to be mediated by ubiquitination promoted by PVM NS proteins. Interestingly, NS proteins of PVM lowered the levels of several ISG (IFN-stimulated gene) proteins as well. These results provide a molecular foundation for the mechanisms by which PVM efficiently subverts the IFN response of the murine cell. They also reveal that in spite of their high sequence dissimilarity, the two pneumoviral NS proteins are functionally and mechanistically similar.
authors.affiliation: Department of Biological, Geological and Environmental Sciences, and Centre for Gene Regulation in Health and Disease, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 44115, USA.
authors.forename: Jayeeta
authors.initials: J
authors.lastname: Dhar
authors.affiliation: Department of Biological, Geological and Environmental Sciences, and Centre for Gene Regulation in Health and Disease, Cleveland State University, 2121 Euclid Avenue, Cleveland, Ohio 44115, USA.
authors.forename: Sailen
authors.initials: S
authors.lastname: Barik
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000276:immunology; D051379:Mice; D029122:Murine pneumonia virus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D018186:Pneumovirus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D059748:Proteolysis; D018357:Respiratory Syncytial Virus Infections / Q000209:etiology; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017361:Viral Nonstructural Proteins; D007372:Interferons