Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy. / Liang, Qiming; Luo, Zhifei; Zeng, Jianxiong; Chen, Weiqiang; Foo, Suan-Sin; Lee, Shin-Ae; Ge, Jianning; Wang, Su; Goldman, Steven A.; Zlokovic, Berislav V; Zhao, Zhen; Jung, Jae U.
In: Cell Stem Cell, Vol. 19, No. 5, 03.11.2016, p. 663-671.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy
AU - Liang, Qiming
AU - Luo, Zhifei
AU - Zeng, Jianxiong
AU - Chen, Weiqiang
AU - Foo, Suan-Sin
AU - Lee, Shin-Ae
AU - Ge, Jianning
AU - Wang, Su
AU - Goldman, Steven A.
AU - Zlokovic, Berislav V
AU - Zhao, Zhen
AU - Jung, Jae U
N1 - Copyright © 2016 Elsevier Inc. All rights reserved.
PY - 2016/11/3
Y1 - 2016/11/3
N2 - The current widespread outbreak of Zika virus (ZIKV) infection has been linked to severe clinical birth defects, particularly microcephaly, warranting urgent study of the molecular mechanisms underlying ZIKV pathogenesis. Akt-mTOR signaling is one of the key cellular pathways essential for brain development and autophagy regulation. Here, we show that ZIKV infection of human fetal neural stem cells (fNSCs) causes inhibition of the Akt-mTOR pathway, leading to defective neurogenesis and aberrant activation of autophagy. By screening the three structural proteins and seven nonstructural proteins present in ZIKV, we found that two, NS4A and NS4B, cooperatively suppress the Akt-mTOR pathway and lead to cellular dysregulation. Corresponding proteins from the closely related dengue virus do not have the same effect on neurogenesis. Thus, our study highlights ZIKV NS4A and NS4B as candidate determinants of viral pathogenesis and identifies a mechanism of action for their effects, suggesting potential targets for anti-ZIKV therapeutic intervention.
AB - The current widespread outbreak of Zika virus (ZIKV) infection has been linked to severe clinical birth defects, particularly microcephaly, warranting urgent study of the molecular mechanisms underlying ZIKV pathogenesis. Akt-mTOR signaling is one of the key cellular pathways essential for brain development and autophagy regulation. Here, we show that ZIKV infection of human fetal neural stem cells (fNSCs) causes inhibition of the Akt-mTOR pathway, leading to defective neurogenesis and aberrant activation of autophagy. By screening the three structural proteins and seven nonstructural proteins present in ZIKV, we found that two, NS4A and NS4B, cooperatively suppress the Akt-mTOR pathway and lead to cellular dysregulation. Corresponding proteins from the closely related dengue virus do not have the same effect on neurogenesis. Thus, our study highlights ZIKV NS4A and NS4B as candidate determinants of viral pathogenesis and identifies a mechanism of action for their effects, suggesting potential targets for anti-ZIKV therapeutic intervention.
U2 - 10.1016/j.stem.2016.07.019
DO - 10.1016/j.stem.2016.07.019
M3 - Journal article
C2 - 27524440
VL - 19
SP - 663
EP - 671
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 5
ER -
ID: 164972167