@article{5ff28cee5cdb457ca9686cbe84f52c57,
title = "An Immunocompetent Mouse Model of Zika Virus Infection",
abstract = " Progress toward understanding Zika virus (ZIKV) pathogenesis is hindered by lack of immunocompetent small animal models, in part because ZIKV fails to effectively antagonize Stat2-dependent interferon (IFN) responses in mice. To address this limitation, we first passaged an African ZIKV strain (ZIKV-Dak-41525) through Rag1 −/− mice to obtain a mouse-adapted virus (ZIKV-Dak-MA) that was more virulent than ZIKV-Dak-41525 in mice treated with an anti-Ifnar1 antibody. A G18R substitution in NS4B was the genetic basis for the increased replication, and resulted in decreased IFN-β production, diminished IFN-stimulated gene expression, and the greater brain infection observed with ZIKV-Dak-MA. To generate a fully immunocompetent mouse model of ZIKV infection, human STAT2 was introduced into the mouse Stat2 locus (hSTAT2 KI). Subcutaneous inoculation of pregnant hSTAT2 KI mice with ZIKV-Dak-MA resulted in spread to the placenta and fetal brain. An immunocompetent mouse model of ZIKV infection may prove valuable for evaluating countermeasures to limit disease. An immunocompetent mouse model of ZIKV infection is needed. Gorman et al. generated ZIKV-Dak-MA, a strain with a mutation in NS4B that causes greater disease in mice than the parental virus. Human STAT2 knockin mice were generated and challenged with ZIKV-Dak-MA to establish a fully immunocompetent ZIKV mouse model.",
keywords = "RNA sequencing, Zika virus, flavivirus, immunity, infectious clone, interferon, pathogenesis, pregnancy, transgenic mice, vertical transmission",
author = "Gorman, {Matthew J.} and Caine, {Elizabeth A.} and Konstantin Zaitsev and Begley, {Matthew C.} and James Weger-Lucarelli and Uccellini, {Melissa B.} and Shashank Tripathi and Juliet Morrison and Yount, {Boyd L.} and Dinnon, {Kenneth H.} and Claudia R{\"u}ckert and Young, {Michael C.} and Zhe Zhu and Robertson, {Shelly J.} and McNally, {Kristin L.} and Jing Ye and Bin Cao and Mysorekar, {Indira U.} and Ebel, {Gregory D.} and Baric, {Ralph S.} and Best, {Sonja M.} and Artyomov, {Maxim N.} and Adolfo Garcia-Sastre and Diamond, {Michael S.}",
note = "Funding Information: We acknowledge the Genome Technology Access Center at Washington University for help with genomic analysis. The center is partially supported by NCI Cancer Center Support Grant P30 CA91842 and by ICTS /CTSA Grant UL1 TR000448 . This work also was supported by grants from the NIH ( R01 AI073755 , R01 AI104972 , and U19 AI083019 to M.S.D.; R01 HD091218 to I.U.M. and M.S.D.; U19 AI118610 and R21 AI129486 to A.G.-S; and R01 AI100625 and R01 AI107810 to R.S.B.) and by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH. K.Z. was supported by Government of Russian Federation grant 074-U01 . Funding Information: We acknowledge the Genome Technology Access Center at Washington University for help with genomic analysis. The center is partially supported by NCI Cancer Center Support Grant P30 CA91842 and by ICTS/CTSA Grant UL1 TR000448. This work also was supported by grants from the NIH (R01 AI073755, R01 AI104972, and U19 AI083019 to M.S.D.; R01 HD091218 to I.U.M. and M.S.D.; U19 AI118610 and R21 AI129486 to A.G.-S; and R01 AI100625 and R01 AI107810 to R.S.B.) and by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH. K.Z. was supported by Government of Russian Federation grant 074-U01. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = may,
day = "9",
doi = "10.1016/j.chom.2018.04.003",
language = "English",
volume = "23",
pages = "672--685.e6",
journal = "Cell Host and Microbe",
issn = "1931-3128",
number = "5",
}