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.