TY - JOUR
T1 - A Mouse Model of Zika Virus Pathogenesis
AU - Lazear, Helen M.
AU - Govero, Jennifer
AU - Smith, Amber M.
AU - Platt, Derek J.
AU - Fernandez, Estefania
AU - Miner, Jonathan J.
AU - Diamond, Michael S.
N1 - Funding Information:
This work was supported by start-up funds from the University of North Carolina Department of Microbiology and Immunology and the Lineberger Comprehensive Cancer Center (H.M.L.), as well as grants from the NIH (R01 AI073755 and R01 AI104972) (M.S.D.). J.J.M., E.F., and D.J.P. were supported by a Rheumatology Research Foundation Scientist Development Award, NIH Pre-Doctoral Training Grant award (T32 AI007163), and NIH Research Education Program (R25 HG006687), respectively. M.S.D. is a consultant for InBios and Visterra and a member of the Scientific Advisory Board of Moderna.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/5/11
Y1 - 2016/5/11
N2 - Summary The ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes, including Guillain-Barré syndrome and birth defects, has brought an urgent need for animal models. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking components of the antiviral response. Four- to six-week-old Irf3-/- Irf5-/- Irf7-/- triple knockout mice, which produce little interferon α/β, and mice lacking the interferon receptor (Ifnar1-/-) developed neurological disease and succumbed to ZIKV infection, whereas single Irf3-/-, Irf5-/-, and Mavs-/- knockout mice exhibited no overt illness. Ifnar1-/- mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The testes of Ifnar1-/- mice had the highest viral loads, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics as well as understanding disease pathogenesis.
AB - Summary The ongoing Zika virus (ZIKV) epidemic and unexpected clinical outcomes, including Guillain-Barré syndrome and birth defects, has brought an urgent need for animal models. We evaluated infection and pathogenesis with contemporary and historical ZIKV strains in immunocompetent mice and mice lacking components of the antiviral response. Four- to six-week-old Irf3-/- Irf5-/- Irf7-/- triple knockout mice, which produce little interferon α/β, and mice lacking the interferon receptor (Ifnar1-/-) developed neurological disease and succumbed to ZIKV infection, whereas single Irf3-/-, Irf5-/-, and Mavs-/- knockout mice exhibited no overt illness. Ifnar1-/- mice sustained high viral loads in the brain and spinal cord, consistent with evidence that ZIKV causes neurodevelopmental defects in human fetuses. The testes of Ifnar1-/- mice had the highest viral loads, which is relevant to sexual transmission of ZIKV. This model of ZIKV pathogenesis will be valuable for evaluating vaccines and therapeutics as well as understanding disease pathogenesis.
UR - http://www.scopus.com/inward/record.url?scp=84962438993&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2016.03.010
DO - 10.1016/j.chom.2016.03.010
M3 - Article
C2 - 27066744
AN - SCOPUS:84962438993
SN - 1931-3128
VL - 19
SP - 720
EP - 730
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 5
ER -