Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways
Abstract Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor a vaccine are available. ZIKV is an enveloped RNA virus, replicating in the cytoplasm in close association with ER membranes. Here, we isolate ER membranes from ZIKV-infected cells and determine their...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-43665-6 |
| _version_ | 1797397914459308032 |
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| author | Solène Denolly Alexey Stukalov Uladzimir Barayeu Alina N. Rosinski Paraskevi Kritsiligkou Sebastian Joecks Tobias P. Dick Andreas Pichlmair Ralf Bartenschlager |
| author_facet | Solène Denolly Alexey Stukalov Uladzimir Barayeu Alina N. Rosinski Paraskevi Kritsiligkou Sebastian Joecks Tobias P. Dick Andreas Pichlmair Ralf Bartenschlager |
| author_sort | Solène Denolly |
| collection | DOAJ |
| description | Abstract Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor a vaccine are available. ZIKV is an enveloped RNA virus, replicating in the cytoplasm in close association with ER membranes. Here, we isolate ER membranes from ZIKV-infected cells and determine their proteome. Forty-six host cell factors are enriched in ZIKV remodeled membranes, several of these having a role in redox and methylation pathways. Four proteins are characterized in detail: thioredoxin reductase 1 (TXNRD1) contributing to folding of disulfide bond containing proteins and modulating ZIKV secretion; aldo-keto reductase family 1 member C3 (AKR1C3), regulating capsid protein abundance and thus, ZIKV assembly; biliverdin reductase B (BLVRB) involved in ZIKV induced lipid peroxidation and increasing stability of viral transmembrane proteins; adenosylhomocysteinase (AHCY) indirectly promoting m6A methylation of ZIKV RNA by decreasing the level of S- adenosyl homocysteine and thus, immune evasion. These results highlight the involvement of redox and methylation enzymes in the ZIKV life cycle and their accumulation at virally remodeled ER membranes. |
| first_indexed | 2024-03-09T01:17:06Z |
| format | Article |
| id | doaj.art-e994d1107b8b43ba817ee5beb730274a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-09T01:17:06Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-e994d1107b8b43ba817ee5beb730274a2023-12-10T12:24:24ZengNature PortfolioNature Communications2041-17232023-12-0114112010.1038/s41467-023-43665-6Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathwaysSolène Denolly0Alexey Stukalov1Uladzimir Barayeu2Alina N. Rosinski3Paraskevi Kritsiligkou4Sebastian Joecks5Tobias P. Dick6Andreas Pichlmair7Ralf Bartenschlager8Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease ResearchTechnical University of Munich, School of Medicine, Institute of VirologyDivision of Redox Regulation, German Cancer Research Center (DKFZ), DKFZ-ZMBH AllianceHeidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease ResearchDivision of Redox Regulation, German Cancer Research Center (DKFZ), DKFZ-ZMBH AllianceHeidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease ResearchDivision of Redox Regulation, German Cancer Research Center (DKFZ), DKFZ-ZMBH AllianceTechnical University of Munich, School of Medicine, Institute of VirologyHeidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease ResearchAbstract Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor a vaccine are available. ZIKV is an enveloped RNA virus, replicating in the cytoplasm in close association with ER membranes. Here, we isolate ER membranes from ZIKV-infected cells and determine their proteome. Forty-six host cell factors are enriched in ZIKV remodeled membranes, several of these having a role in redox and methylation pathways. Four proteins are characterized in detail: thioredoxin reductase 1 (TXNRD1) contributing to folding of disulfide bond containing proteins and modulating ZIKV secretion; aldo-keto reductase family 1 member C3 (AKR1C3), regulating capsid protein abundance and thus, ZIKV assembly; biliverdin reductase B (BLVRB) involved in ZIKV induced lipid peroxidation and increasing stability of viral transmembrane proteins; adenosylhomocysteinase (AHCY) indirectly promoting m6A methylation of ZIKV RNA by decreasing the level of S- adenosyl homocysteine and thus, immune evasion. These results highlight the involvement of redox and methylation enzymes in the ZIKV life cycle and their accumulation at virally remodeled ER membranes.https://doi.org/10.1038/s41467-023-43665-6 |
| spellingShingle | Solène Denolly Alexey Stukalov Uladzimir Barayeu Alina N. Rosinski Paraskevi Kritsiligkou Sebastian Joecks Tobias P. Dick Andreas Pichlmair Ralf Bartenschlager Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways Nature Communications |
| title | Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways |
| title_full | Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways |
| title_fullStr | Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways |
| title_full_unstemmed | Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways |
| title_short | Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways |
| title_sort | zika virus remodelled er membranes contain proviral factors involved in redox and methylation pathways |
| url | https://doi.org/10.1038/s41467-023-43665-6 |
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