An Immunocompetent Mouse Model of Zika Virus Infection

被引：180

作者：

Gorman, Matthew J. ^{[1
]}

Caine, Elizabeth A. ^{[2
]}

Zaitsev, Konstantin ^{[1
,14
]}

Begley, Matthew C. ^{[6
,7
]}

Weger-Lucarelli, James ^{[8
]}

Uccellini, Melissa B. ^{[9
,11
]}

Tripathi, Shashank ^{[9
,11
]}

Morrison, Juliet ^{[9
]}

Yount, Boyd L. ^{[6
,7
]}

Dinnon, Kenneth H., III ^{[6
,7
]}

Ruckert, Claudia ^{[8
]}

Young, Michael C. ^{[8
]}

Zhu, Zhe ^{[12
]}

Robertson, Shelly J. ^{[13
]}

McNally, Kristin L. ^{[13
]}

Ye, Jing ^{[2
]}

Cao, Bin ^{[4
]}

Mysorekar, Indira U. ^{[1
,4
]}

Ebel, Gregory D. ^{[8
]}

Baric, Ralph S. ^{[6
,7
]}

Best, Sonja M. ^{[13
]}

Artyomov, Maxim N. ^{[1
,5
]}

Garcia-Sastre, Adolfo ^{[9
,10
,11
]}

Diamond, Michael S. ^{[1
,2
,3
,5
]}

机构：

[1] Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63130 USA

[2] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Ctr Human Immunol & Immunotherapy Programs, St Louis, MO 63130 USA

[6] Univ North Carolina Chapel Hill, Dept Microbiol & Immunol, Chapel Hill, NC USA

[7] Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA

[8] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA

[9] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[10] Icahn Sch Med Mt Sinai, Div Infect Dis, Dept Med, New York, NY 10029 USA

[11] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA

[12] Univ Calif San Diego, Sch Med, Dept Med, Div Regenerat Med, La Jolla, CA 92093 USA

[13] NIAID, Lab Virol, Rocky Mt Labs, NIH, Hamilton, MT USA

[14] ITMO Univ, Comp Technol Dept, St Petersburg, Russia

来源：

CELL HOST & MICROBE | 2018年 / 23卷 / 05期

关键词：

NEURAL STEM-CELLS; GLIAL-CELLS; NS4B; HETEROGENEITY; PATHOGENESIS; REPLICATION; ANTIBODY; PROTEIN; BRAIN; LEADS;

D O I：

10.1016/j.chom.2018.04.003

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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-beta 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.

引用

页码：672 / +

页数：20

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