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Article: Targeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations

TitleTargeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations
Authors
KeywordsZika virus
IRE1
UPR
Neurogenesis
Spermatogenesis
Issue Date2020
PublisherAmerican 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?
AbstractZika 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 Identifierhttp://hdl.handle.net/10722/286254
ISSN
2019 Impact Factor: 4.614

 

DC FieldValueLanguage
dc.contributor.authorChu, H-
dc.contributor.authorYuen, TTT-
dc.contributor.authorChik, KKH-
dc.contributor.authorYuan, S-
dc.contributor.authorShuai, H-
dc.contributor.authorZou, Z-
dc.contributor.authorWang, Y-
dc.contributor.authorZhu, Z-
dc.contributor.authorYang, D-
dc.contributor.authorPoon, VKM-
dc.contributor.authorChan, CCS-
dc.contributor.authorZhou, J-
dc.contributor.authorYin, F-
dc.contributor.authorKok, KH-
dc.contributor.authorYuen, KY-
dc.contributor.authorChan, JFW-
dc.date.accessioned2020-08-31T07:01:21Z-
dc.date.available2020-08-31T07:01:21Z-
dc.date.issued2020-
dc.identifier.citationACS Infectious Diseases, 2020, v. 6 n. 7, p. 1745-1758-
dc.identifier.issn2373-8227-
dc.identifier.urihttp://hdl.handle.net/10722/286254-
dc.description.abstractZika 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.languageeng-
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journal/aidcbc-
dc.relation.ispartofACS Infectious Diseases-
dc.subjectZika virus-
dc.subjectIRE1-
dc.subjectUPR-
dc.subjectNeurogenesis-
dc.subjectSpermatogenesis-
dc.titleTargeting the Inositol-Requiring Enzyme-1 Pathway Efficiently Reverts Zika Virus-Induced Neurogenesis and Spermatogenesis Marker Perturbations-
dc.typeArticle-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailShuai, H: shuaihp@connect.hku.hk-
dc.identifier.emailPoon, VKM: vinpoon@hku.hk-
dc.identifier.emailChan, CCS: cschan@hku.hk-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailKok, KH: khkok@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityYuan, S=rp02640-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityChan, JFW=rp01736-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1021/acsinfecdis.9b00526-
dc.identifier.pmid32329611-
dc.identifier.scopuseid_2-s2.0-85088485913-
dc.identifier.hkuros313105-
dc.identifier.volume6-
dc.identifier.issue7-
dc.identifier.spage1745-
dc.identifier.epage1758-
dc.publisher.placeUnited States-

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