Tweet
Zika Virus NS4A and NS4B Proteins Deregulate Akt-mTOR Signaling in Human Fetal Neural Stem Cells to Inhibit Neurogenesis and Induce Autophagy
Qiming LiangcorrespondencePress enter key for correspondence informationemailPress enter key to Email the author, Zhifei Luo, Jianxiong Zeng, Weiqiang Chen, Suan-Sin Foo, Shin-Ae Lee, Jianning Ge, Su Wang, Steven A. Goldman, Berislav V. Zlokovic, Zhen ZhaocorrespondencePress enter key for correspondence informationemailPress enter key to Email the author, Jae U. Jung8,correspondencePress enter key for correspondence informationemailPress enter key to Email the author
8Lead Contact
Publication stage: In Press Corrected Proof
DOI: http://dx.doi.org/10.1016/j.stem.2016.07.019
showArticle Info
Introduction
Zika virus (ZIKV), a reemerging arthropod-bone flavivirus, was initially isolated from Rhesus macaque in Uganda as early as 1947, while the first human infection was reported in 1954 (Dick, 1952, Dick et al., 1952, Simpson, 1964). Although sexually transmitted cases have been recently documented, ZIKV is most commonly transmitted through the bites of infected Aedes mosquitoes (Musso et al., 2015, Venturi et al., 2016). Individuals infected by ZIKV typically develop a mild or unapparent dengue-like disease (Duffy et al., 2009). However, mounting evidence has linked ZIKV infection to neurological defects in newborns (De Carvalho et al., 2016). Furthermore, ZIKV was detected in the amniotic fluids of pregnant women as well as in the brain tissues of microcephalic fetuses, suggesting that ZIKV can potentially cross the placental barrier to infect fetuses (Calvet et al., 2016, Mlakar et al., 2016). In addition, an increased rate of Guillain-Barr? syndrome was noted following the ZIKV outbreak in French Polynesia from 2013 to 2014 (Cauchemez et al., 2016). The World Health Organization declared a Public Health Emergency of International Concern (Heymann et al., 2016), and the Centers for Disease Control and Prevention confirmed that ZIKV causes microcephaly and other birth defects. Although ZIKV infection impairs the growth of neurospheres and brain organoids derived from iPSCs (Garcez et al., 2016, Qian et al., 2016), the molecular mechanism by which ZIKV infection induces fetal microcephaly remains elusive. In particular, dengue virus (DENV), a closely related member of the flaviviridae family, has not been linked to either microcephaly or defects in neurogenesis (Garcez et al., 2016), suggesting that ZIKV?s neuropathology might be causally linked to those differences in its sequence from dengue.
...
Qiming LiangcorrespondencePress enter key for correspondence informationemailPress enter key to Email the author, Zhifei Luo, Jianxiong Zeng, Weiqiang Chen, Suan-Sin Foo, Shin-Ae Lee, Jianning Ge, Su Wang, Steven A. Goldman, Berislav V. Zlokovic, Zhen ZhaocorrespondencePress enter key for correspondence informationemailPress enter key to Email the author, Jae U. Jung8,correspondencePress enter key for correspondence informationemailPress enter key to Email the author
8Lead Contact
Publication stage: In Press Corrected Proof
DOI: http://dx.doi.org/10.1016/j.stem.2016.07.019
showArticle Info
Introduction
Zika virus (ZIKV), a reemerging arthropod-bone flavivirus, was initially isolated from Rhesus macaque in Uganda as early as 1947, while the first human infection was reported in 1954 (Dick, 1952, Dick et al., 1952, Simpson, 1964). Although sexually transmitted cases have been recently documented, ZIKV is most commonly transmitted through the bites of infected Aedes mosquitoes (Musso et al., 2015, Venturi et al., 2016). Individuals infected by ZIKV typically develop a mild or unapparent dengue-like disease (Duffy et al., 2009). However, mounting evidence has linked ZIKV infection to neurological defects in newborns (De Carvalho et al., 2016). Furthermore, ZIKV was detected in the amniotic fluids of pregnant women as well as in the brain tissues of microcephalic fetuses, suggesting that ZIKV can potentially cross the placental barrier to infect fetuses (Calvet et al., 2016, Mlakar et al., 2016). In addition, an increased rate of Guillain-Barr? syndrome was noted following the ZIKV outbreak in French Polynesia from 2013 to 2014 (Cauchemez et al., 2016). The World Health Organization declared a Public Health Emergency of International Concern (Heymann et al., 2016), and the Centers for Disease Control and Prevention confirmed that ZIKV causes microcephaly and other birth defects. Although ZIKV infection impairs the growth of neurospheres and brain organoids derived from iPSCs (Garcez et al., 2016, Qian et al., 2016), the molecular mechanism by which ZIKV infection induces fetal microcephaly remains elusive. In particular, dengue virus (DENV), a closely related member of the flaviviridae family, has not been linked to either microcephaly or defects in neurogenesis (Garcez et al., 2016), suggesting that ZIKV?s neuropathology might be causally linked to those differences in its sequence from dengue.
...
Comment