RGD Reference Report - An Immunocompetent Mouse Model of Zika Virus Infection. - Rat Genome Database

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An Immunocompetent Mouse Model of Zika Virus Infection.

Authors: Gorman, Matthew J  Caine, Elizabeth A  Zaitsev, Konstantin  Begley, Matthew C  Weger-Lucarelli, James  Uccellini, Melissa B  Tripathi, Shashank  Morrison, Juliet  Yount, Boyd L  Dinnon, Kenneth H  Rückert, Claudia  Young, Michael C  Zhu, Zhe  Robertson, Shelly J  McNally, Kristin L  Ye, Jing  Cao, Bin  Mysorekar, Indira U  Ebel, Gregory D  Baric, Ralph S  Best, Sonja M  Artyomov, Maxim N  Garcia-Sastre, Adolfo  Diamond, Michael S 
Citation: Gorman MJ, etal., Cell Host Microbe. 2018 May 9;23(5):672-685.e6. doi: 10.1016/j.chom.2018.04.003.
RGD ID: 41789627
Pubmed: (View Article at PubMed) PMID:29746837
DOI: Full-text: DOI:10.1016/j.chom.2018.04.003

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.

Annotation

Disease Annotations    
Zika fever  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Stat2  (signal transducer and activator of transcription 2)

Genes (Mus musculus)
Stat2  (signal transducer and activator of transcription 2)

Genes (Homo sapiens)
STAT2  (signal transducer and activator of transcription 2)


Additional Information