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Article: Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy
Title | Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy |
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Authors | |
Keywords | Antiviral Flavivirus Inhibitor Interferon NS5 |
Issue Date | 2019 |
Publisher | Molecular 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? |
Abstract | Post-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 Identifier | http://hdl.handle.net/10722/274574 |
ISSN | 2023 Impact Factor: 4.9 2023 SCImago Journal Rankings: 1.179 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Zhu, Z | - |
dc.contributor.author | Chu, H | - |
dc.contributor.author | Wen, L | - |
dc.contributor.author | Yuan, S | - |
dc.contributor.author | Chik, KKH | - |
dc.contributor.author | Yuen, TT | - |
dc.contributor.author | Yip, CY | - |
dc.contributor.author | Wang, D | - |
dc.contributor.author | Zhou, J | - |
dc.contributor.author | Yin, F | - |
dc.contributor.author | Jin, D | - |
dc.contributor.author | Kok, KH | - |
dc.contributor.author | Yuen, KY | - |
dc.contributor.author | Chan, JFW | - |
dc.date.accessioned | 2019-08-18T15:04:28Z | - |
dc.date.available | 2019-08-18T15:04:28Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | International Journal of Molecular Sciences, 2019, v. 20 n. 2, article no. 392 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | http://hdl.handle.net/10722/274574 | - |
dc.description.abstract | Post-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.language | eng | - |
dc.publisher | Molecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms | - |
dc.relation.ispartof | International Journal of Molecular Sciences | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Antiviral | - |
dc.subject | Flavivirus | - |
dc.subject | Inhibitor | - |
dc.subject | Interferon | - |
dc.subject | NS5 | - |
dc.title | Targeting SUMO Modification of the Non-Structural Protein 5 of Zika Virus as a Host-Targeting Antiviral Strategy | - |
dc.type | Article | - |
dc.identifier.email | Chu, H: hinchu@hku.hk | - |
dc.identifier.email | Yuan, S: yuansf@hku.hk | - |
dc.identifier.email | Yip, CY: yipcyril@hku.hk | - |
dc.identifier.email | Zhou, J: jiezhou@hku.hk | - |
dc.identifier.email | Jin, D: dyjin@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 | Yip, CY=rp01721 | - |
dc.identifier.authority | Zhou, J=rp01412 | - |
dc.identifier.authority | Jin, D=rp00452 | - |
dc.identifier.authority | Kok, KH=rp01455 | - |
dc.identifier.authority | Yuen, KY=rp00366 | - |
dc.identifier.authority | Chan, JFW=rp01736 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3390/ijms20020392 | - |
dc.identifier.pmid | 30658479 | - |
dc.identifier.pmcid | PMC6359730 | - |
dc.identifier.scopus | eid_2-s2.0-85060124105 | - |
dc.identifier.hkuros | 301250 | - |
dc.identifier.volume | 20 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | article no. 392 | - |
dc.identifier.epage | article no. 392 | - |
dc.identifier.isi | WOS:000459746500160 | - |
dc.publisher.place | Switzerland | - |
dc.identifier.issnl | 1422-0067 | - |