title: Partial dysfunction of STAT1 profoundly reduces host resistance to flaviviral infection.
abstract: The genetic basis for a dramatically increased virus susceptibility phenotype of MHC-II knockout mice acquired during routine maintenance of the mouse strain was determined. Segregation of the susceptibility allele from the defective MHC-II locus combined with sequence capture and sequencing showed that a Y37L substitution in STAT1 accounted for high flavivirus susceptibility of a newly derived mouse strain, designated Tuara. Interestingly, the mutation in STAT1 gene gave only partial inactivation of the type I interferon antiviral pathway. Accordingly, merely a relatively small impairment of interferon α/β signalling is sufficient to overcome the ability of the host to control the infection.
authors.affiliation: Department of Emerging Pathogens and Vaccines, John Curtin School of Medical Research, The Australian National University, Canberra, Australia; Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: maximilian.larena@gu.se.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Larena
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia.
authors.forename: Mario
authors.initials: M
authors.lastname: Lobigs
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D018067:Flaviviridae / Q000235:genetics / Q000502:physiology*; D018178:Flaviviridae Infections / Q000235:genetics / Q000276:immunology / Q000821:virology*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D050794:STAT1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D007370:Interferon Type I; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse
keywords: Flavivirus; Genetic mapping; Interferon; Japanese encephalitis virus; STAT1; Spontaneous mutation; West nile virus