| First Author | Gorman MJ | Year | 2018 |
| Journal | Cell Host Microbe | Volume | 23 |
| Issue | 5 | Pages | 672-685.e6 |
| PubMed ID | 29746837 | Mgi Jnum | J:261503 |
| Mgi Id | MGI:6156514 | Doi | 10.1016/j.chom.2018.04.003 |
| Citation | Gorman MJ, et al. (2018) An Immunocompetent Mouse Model of Zika Virus Infection. Cell Host Microbe 23(5):672-685.e6 |
| abstractText | 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. |
