Mice

Animal studies were carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocols were approved by the Institutional Animal Care and Use Committee at the Washington University School of Medicine. Virus inoculations were performed under anesthesia that was induced and maintained with ketamine hydrochloride and xylazine, and all efforts were made to minimize animal suffering. WT C57BL/6J (#000664) mice were obtained from The Jackson Laboratory or bred in a pathogen-free animal facility at Washington University. Ifnlr1 ^−/− (Ank et al., 2008) and Ifnl2-gfp reporter mice (Galani et al., 2017) (generated by Evangelos Andreakos and kindly provided by Megan Baldridge, Washington University) were bred and housed in a pathogen-free animal facility at Washington University. Heterozygous K18-hACE C57BL/6J mice (strain: 2B6.Cg-Tg(K18-ACE2)2Prlmn/J) were obtained from The Jackson Laboratory. 129S2 mice were obtained from Charles River. Animals were housed in groups and fed standard chow diets. The ages and sex of mice used in this study were as follows: (a) six-week-old or three-month-old male and female WT and Ifnlr1 ^−/− C57BL/6 mice; (b) eight-week-old or five-month-old female K18-hACE2 mice; (c) six-week-old female 129S2 mice; and (d) six-week-old male and female Mavs ^−/−, cGas ^−/−, Myd88 ^−/− or WT C57BL/6 mice.