Zika virus infection in Collaborative Cross mice

Abstract

14The 2015-2016 emergence of Zika virus (ZIKV) in the Americas, and recognition that ZIKV 15 infection during pregnancy can result in birth defects, revealed a need for small animal models to 16 study ZIKV pathogenic mechanisms and evaluate candidate vaccines and antivirals. Mice would 17 be an attractive system for such studies, but ZIKV replicates poorly in laboratory mice because it 18 fails to antagonize murine STAT2 and STING. To address this, most ZIKV pathogenesis studies 19 have used mice with impaired interferon signaling (e.g. Ifnar1 -/or treatment with IFNAR1-blocking 20 antibodies). However, using mice with severe defects in innate antiviral signaling confounds 21 studies of viral pathogenic mechanisms. Collaborative Cross (CC) mice have proven to be a 22valuable system for developing new mouse pathogenesis models for viral infections that are not 23 well modeled in conventional laboratory mouse lines. To test whether CC mice could provide an 24 immune-competent model for ZIKV pathogenesis, we infected CC lines with ZIKV and assessed 25 weight loss, viremia, and production of neutralizing antibodies. We tested 21 CC lines (CC001, 26 All rights reserved. No reuse allowed without permission.