title: Mice lacking the ISG15 E1 enzyme UbE1L demonstrate increased susceptibility to both mouse-adapted and non-mouse-adapted influenza B virus infection.
abstract: ISG15 functions as a critical antiviral molecule against influenza virus, with infection inducing both the conjugation of ISG15 to target proteins and production of free ISG15. Here, we report that mice lacking the ISG15 E1 enzyme UbE1L fail to form ISG15 conjugates. Both UbE1L(-/-) and ISG15(-/-) mice display increased susceptibility to influenza B virus infection, including non-mouse-adapted strains. Finally, we demonstrate that ISG15 controls influenza B virus infection through its action within radioresistant stromal cells and not bone marrow-derived cells. Thus, the conjugation of ISG15 to target proteins within stromal cells is critical to its activity against influenza virus.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lai
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Struckhoff
authors.forename: Jana
authors.initials: J
authors.lastname: Schneider
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Sobrido
authors.forename: Thorsten
authors.initials: T
authors.lastname: Wolff
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Dong-Er
authors.initials: DE
authors.lastname: Zhang
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Lenschow
mesh_terms: D000818:Animals; D016207:Cytokines / Q000172:deficiency*; D020022:Genetic Predisposition to Disease; D009981:Influenza B virus / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D016019:Survival Analysis; D044764:Ubiquitin-Activating Enzymes / Q000172:deficiency*; D014452:Ubiquitins / Q000172:deficiency
chemical_list: D016207:Cytokines; C489550:G1p2 protein, mouse; D014452:Ubiquitins; D044764:Ubiquitin-Activating Enzymes