title: Murine gammaherpesvirus targets type I IFN receptor but not type III IFN receptor early in infection.
abstract: The innate immune response represents a primary line of defense against invading viral pathogens. Since epithelial cells are the primary site of gammaherpesvirus replication during infection in vivo and there are no information on activity of IFN-III signaling against gammaherpesviruses in this cell type, in present study, we evaluated the expression profile and virus-host interactions in mouse mammary epithelial cell (NMuMG) infected with three strains of murine gammaherpesvirus, MHV-68, MHV-72 and MHV-4556. Studying three strains of murine gammaherpesvirus, which differ in nucleotide sequence of some structural and non-structural genes, allowed us to compare the strain-dependent interactions with host organism. Our results clearly demonstrate that: (i) MHV-68, MHV-72 and MHV-4556 differentially interact with intracellular signaling and dysregulate IFN signal transduction; (ii) MHV-68, MHV-72 and MHV-4556 degrade type I IFN receptor in very early stages of infection (2-4hpi), but not type III IFN receptor; (iii) type III IFN signaling might play a key role in antiviral defense of epithelial cells in early stages of murine gammaherpesvirus replication; (iv) NMuMG cells are an appropriate model for study of not only type I IFN signaling, but also type III IFN signaling pathway. These findings are important for better understanding of individual virus-host interactions in lytic as well as in persistent gammaherpesvirus replication and help us to elucidate IFN-III function in early events of virus infection.
authors.affiliation: Institute of Virology, Biomedical Research Center of Slovak Academy of Sciences, Bratislava 845 05, Slovak Republic.
authors.forename: Katarína
authors.initials: K
authors.lastname: Lopušná
authors.affiliation: Institute of Virology, Biomedical Research Center of Slovak Academy of Sciences, Bratislava 845 05, Slovak Republic.
authors.forename: Tímea
authors.initials: T
authors.lastname: Benkóczka
authors.affiliation: School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
authors.forename: Jakub
authors.initials: J
authors.lastname: Lupták
authors.affiliation: Institute of Virology, Biomedical Research Center of Slovak Academy of Sciences, Bratislava 845 05, Slovak Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Matúšková
authors.affiliation: Institute of Virology, Biomedical Research Center of Slovak Academy of Sciences, Bratislava 845 05, Slovak Republic.
authors.forename: Ľubomíra
authors.initials: Ľ
authors.lastname: Lukáčiková
authors.affiliation: Institute of Virology, Biomedical Research Center of Slovak Academy of Sciences, Bratislava 845 05, Slovak Republic.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Ovečková
authors.affiliation: Institute of Virology, Biomedical Research Center of Slovak Academy of Sciences, Bratislava 845 05, Slovak Republic. Electronic address: viruorav@savba.sk.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Režuchová
mesh_terms: D000818:Animals; D018142:Gammaherpesvirinae / Q000235:genetics / Q000378:metabolism*; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000067996:RAW 264.7 Cells; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D053633:Receptor, Interferon alpha-beta
keywords: Interferon lambda; Interferon type I; Interferon-stimulated gene; MHV-68; Murine gammaherpesvirus