The differential interferon responses of two strains of Stat1-deficient mice do not alter susceptibility to HSV-1 and VSV in vivo

Stat1 is a pivotal transcription factor for generation of the interferon (IFN)-dependent antiviral response. Two Stat1 knockout mouse lines have been previously generated, one deleted the N-terminal domain (Delta NTD) and one in the DNA-binding domain (Delta DBD). These widely-used strains are assumed interchangeable, and both are highly susceptible to various pathogens. In this study, primary cells derived from Delta NTD mice were shown to be significantly more responsive to IFN, and established an antiviral state with greater efficiency than cells derived from Delta DBD mice, following infection with vesicular stomatitis virus and herpes simplex virus type-1. Also, while mice from both strains succumbed rapidly and equally to virus infection, Delta DBD mice supported significantly higher replication in brains and livers than Delta NTD mice. Endpoint-type experimental comparisons of these mouse strains are therefore misleading in failing to indicate important differences in virus replication and innate response. (C) 2013 Elsevier Inc. All rights reserved.