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Article: Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy

TitleTargeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy
Authors
KeywordsAntiviral
Flavivirus
Inhibitor
Interferon
NS5
Issue Date2019
PublisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms
Citation
International Journal of Molecular Sciences, 2019, v. 20 n. 2, article no. 392 How to Cite?
AbstractPost-translational modifications of host or viral proteins are key strategies exploited by viruses to support virus replication and counteract host immune response. SUMOylation is a post-translational modification process mediated by a family of ubiquitin-like proteins called small ubiquitin-like modifier (SUMO) proteins. Multiple sequence alignment of 78 representative flaviviruses showed that most (72/78, 92.3%) have a putative SUMO-interacting motif (SIM) at their non-structural 5 (NS5) protein's N-terminal domain. The putative SIM was highly conserved among 414 pre-epidemic and epidemic Zika virus (ZIKV) strains, with all of them having a putative SIM core amino acid sequence of VIDL (327/414, 79.0%) or VVDL (87/414, 21.0%). Molecular docking predicted that the hydrophobic SIM core residues bind to the 2 strand of the SUMO-1 protein, and the acidic residues flanking the core strengthen the binding through interactions with the basic surface of the SUMO protein. The SUMO inhibitor 2-D08 significantly reduced replication of flaviviruses and protected cells against ZIKV-induced cytopathic effects in vitro. A SIM-mutated ZIKV NS5 failed to efficiently suppress type I interferon signaling. Overall, these findings may suggest SUMO modification of the viral NS5 protein to be an evolutionarily conserved post-translational modification process among flaviviruses to enhance virus replication and suppress host antiviral response.
Persistent Identifierhttp://hdl.handle.net/10722/274574
ISSN
2011 Impact Factor: 2.598
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhu, Z-
dc.contributor.authorChu, H-
dc.contributor.authorWen, L-
dc.contributor.authorYuan, S-
dc.contributor.authorChik, KKH-
dc.contributor.authorYuen, TT-
dc.contributor.authorYip, CY-
dc.contributor.authorWang, D-
dc.contributor.authorZhou, J-
dc.contributor.authorYin, F-
dc.contributor.authorJin, D-
dc.contributor.authorKok, KH-
dc.contributor.authorYuen, KY-
dc.contributor.authorChan, JFW-
dc.date.accessioned2019-08-18T15:04:28Z-
dc.date.available2019-08-18T15:04:28Z-
dc.date.issued2019-
dc.identifier.citationInternational Journal of Molecular Sciences, 2019, v. 20 n. 2, article no. 392-
dc.identifier.issn1661-6596-
dc.identifier.urihttp://hdl.handle.net/10722/274574-
dc.description.abstractPost-translational modifications of host or viral proteins are key strategies exploited by viruses to support virus replication and counteract host immune response. SUMOylation is a post-translational modification process mediated by a family of ubiquitin-like proteins called small ubiquitin-like modifier (SUMO) proteins. Multiple sequence alignment of 78 representative flaviviruses showed that most (72/78, 92.3%) have a putative SUMO-interacting motif (SIM) at their non-structural 5 (NS5) protein's N-terminal domain. The putative SIM was highly conserved among 414 pre-epidemic and epidemic Zika virus (ZIKV) strains, with all of them having a putative SIM core amino acid sequence of VIDL (327/414, 79.0%) or VVDL (87/414, 21.0%). Molecular docking predicted that the hydrophobic SIM core residues bind to the 2 strand of the SUMO-1 protein, and the acidic residues flanking the core strengthen the binding through interactions with the basic surface of the SUMO protein. The SUMO inhibitor 2-D08 significantly reduced replication of flaviviruses and protected cells against ZIKV-induced cytopathic effects in vitro. A SIM-mutated ZIKV NS5 failed to efficiently suppress type I interferon signaling. Overall, these findings may suggest SUMO modification of the viral NS5 protein to be an evolutionarily conserved post-translational modification process among flaviviruses to enhance virus replication and suppress host antiviral response.-
dc.languageeng-
dc.publisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms-
dc.relation.ispartofInternational Journal of Molecular Sciences-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAntiviral-
dc.subjectFlavivirus-
dc.subjectInhibitor-
dc.subjectInterferon-
dc.subjectNS5-
dc.titleTargeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy-
dc.typeArticle-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailYip, CY: yipcyril@hku.hk-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailJin, D: dyjin@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.authorityYip, CY=rp01721-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityJin, D=rp00452-
dc.identifier.authorityKok, KH=rp01455-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityChan, JFW=rp01736-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/ijms20020392-
dc.identifier.pmid30658479-
dc.identifier.scopuseid_2-s2.0-85060124105-
dc.identifier.hkuros301250-
dc.identifier.volume20-
dc.identifier.issue2-
dc.identifier.spagearticle no. 392-
dc.identifier.epagearticle no. 392-
dc.identifier.isiWOS:000459746500160-
dc.publisher.placeSwitzerland-

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