|
Basic Characteristics of Mutations
|
|
Mutation Site
|
K399R |
|
Mutation Site Sentence
|
ZIKV-Dak-MA had three mutations present in over 95% of the viral population, two of which (NS3 K399R and NS4B G18R) were non-synonymous changes. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
NS3 |
|
Standardized Encoding Gene
|
NS3
|
|
Genotype/Subtype
|
- |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Zika virus infection
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
29746837
|
|
Title
|
An Immunocompetent Mouse Model of Zika Virus Infection
|
|
Author
|
Gorman MJ,Caine EA,Zaitsev K,Begley MC,Weger-Lucarelli J,Uccellini MB,Tripathi S,Morrison J,Yount BL,Dinnon KH 3rd,Ruckert C,Young MC,Zhu Z,Robertson SJ,McNally KL,Ye J,Cao B,Mysorekar IU,Ebel GD,Baric RS,Best SM,Artyomov MN,Garcia-Sastre A,Diamond MS
|
|
Journal
|
Cell host & microbe
|
|
Journal Info
|
2018 May 9;23(5):672-685
|
|
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-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.
|
|
Sequence Data
|
KU955591.1
|
|
|