File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1021/acsinfecdis.9b00526
- Scopus: eid_2-s2.0-85088485913
- PMID: 32329611
- WOS: WOS:000595290900025
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Targeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations
Title | Targeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations |
---|---|
Authors | |
Keywords | Zika virus IRE1 UPR Neurogenesis Spermatogenesis |
Issue Date | 2020 |
Publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/journal/aidcbc |
Citation | ACS Infectious Diseases, 2020, v. 6 n. 7, p. 1745-1758 How to Cite? |
Abstract | Zika virus (ZIKV) is an emerging flavivirus that may be associated with congenital anomalies in infected fetuses and severe neurological and genital tract complications in infected adults. Currently, antiviral treatments to revert these ZIKV-induced complications are lacking. ZIKV infection has recently been suggested to upregulate the host unfolded protein response, which may contribute to the congenital neurological anomalies. As an extension from these findings, we thoroughly investigated the ZIKV-induced unfolded protein response using a combination of the neuronal cell line, induced pluripotent stem cell-derived human neuronal stem and progenitor cells, and an interferon receptor-deficient A129 mouse model. Our results revealed a critical contribution of the inositol-requiring enzyme-1 (IRE1) arm of the unfolded protein response to ZIKV-induced neurological and testicular complications. Importantly, the inhibition of the IRE1 signaling pathway activation with KIRA6 (kinase-inhibiting RNAse attenuator 6), a selective small molecule IRE1 inhibitor that promotes cell survival, potently reverted the ZIKV-induced perturbations of the key gene expressions associated with neurogenesis and spermatogenesis in vitro and in vivo, highlighting the potential of IRE1 inhibition as a novel host-targeting antiviral strategy in combating against ZIKV-induced neurological and testicular pathologies. |
Persistent Identifier | http://hdl.handle.net/10722/286254 |
ISSN | 2023 Impact Factor: 4.0 2023 SCImago Journal Rankings: 1.179 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chu, H | - |
dc.contributor.author | Yuen, TTT | - |
dc.contributor.author | Chik, KKH | - |
dc.contributor.author | Yuan, S | - |
dc.contributor.author | Shuai, H | - |
dc.contributor.author | Zou, Z | - |
dc.contributor.author | Wang, Y | - |
dc.contributor.author | Zhu, Z | - |
dc.contributor.author | Yang, D | - |
dc.contributor.author | Poon, VKM | - |
dc.contributor.author | Chan, CCS | - |
dc.contributor.author | Zhou, J | - |
dc.contributor.author | Yin, F | - |
dc.contributor.author | Kok, KH | - |
dc.contributor.author | Yuen, KY | - |
dc.contributor.author | Chan, JFW | - |
dc.date.accessioned | 2020-08-31T07:01:21Z | - |
dc.date.available | 2020-08-31T07:01:21Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | ACS Infectious Diseases, 2020, v. 6 n. 7, p. 1745-1758 | - |
dc.identifier.issn | 2373-8227 | - |
dc.identifier.uri | http://hdl.handle.net/10722/286254 | - |
dc.description.abstract | Zika virus (ZIKV) is an emerging flavivirus that may be associated with congenital anomalies in infected fetuses and severe neurological and genital tract complications in infected adults. Currently, antiviral treatments to revert these ZIKV-induced complications are lacking. ZIKV infection has recently been suggested to upregulate the host unfolded protein response, which may contribute to the congenital neurological anomalies. As an extension from these findings, we thoroughly investigated the ZIKV-induced unfolded protein response using a combination of the neuronal cell line, induced pluripotent stem cell-derived human neuronal stem and progenitor cells, and an interferon receptor-deficient A129 mouse model. Our results revealed a critical contribution of the inositol-requiring enzyme-1 (IRE1) arm of the unfolded protein response to ZIKV-induced neurological and testicular complications. Importantly, the inhibition of the IRE1 signaling pathway activation with KIRA6 (kinase-inhibiting RNAse attenuator 6), a selective small molecule IRE1 inhibitor that promotes cell survival, potently reverted the ZIKV-induced perturbations of the key gene expressions associated with neurogenesis and spermatogenesis in vitro and in vivo, highlighting the potential of IRE1 inhibition as a novel host-targeting antiviral strategy in combating against ZIKV-induced neurological and testicular pathologies. | - |
dc.language | eng | - |
dc.publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/journal/aidcbc | - |
dc.relation.ispartof | ACS Infectious Diseases | - |
dc.subject | Zika virus | - |
dc.subject | IRE1 | - |
dc.subject | UPR | - |
dc.subject | Neurogenesis | - |
dc.subject | Spermatogenesis | - |
dc.title | Targeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations | - |
dc.type | Article | - |
dc.identifier.email | Chu, H: hinchu@hku.hk | - |
dc.identifier.email | Yuan, S: yuansf@hku.hk | - |
dc.identifier.email | Shuai, H: shuaihp@connect.hku.hk | - |
dc.identifier.email | Poon, VKM: vinpoon@hku.hk | - |
dc.identifier.email | Chan, CCS: cschan@hku.hk | - |
dc.identifier.email | Zhou, J: jiezhou@hku.hk | - |
dc.identifier.email | Kok, KH: khkok@hku.hk | - |
dc.identifier.email | Yuen, KY: kyyuen@hkucc.hku.hk | - |
dc.identifier.email | Chan, JFW: jfwchan@hku.hk | - |
dc.identifier.authority | Chu, H=rp02125 | - |
dc.identifier.authority | Yuan, S=rp02640 | - |
dc.identifier.authority | Zhou, J=rp01412 | - |
dc.identifier.authority | Kok, KH=rp01455 | - |
dc.identifier.authority | Yuen, KY=rp00366 | - |
dc.identifier.authority | Chan, JFW=rp01736 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1021/acsinfecdis.9b00526 | - |
dc.identifier.pmid | 32329611 | - |
dc.identifier.scopus | eid_2-s2.0-85088485913 | - |
dc.identifier.hkuros | 313105 | - |
dc.identifier.volume | 6 | - |
dc.identifier.issue | 7 | - |
dc.identifier.spage | 1745 | - |
dc.identifier.epage | 1758 | - |
dc.identifier.isi | WOS:000595290900025 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 2373-8227 | - |