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Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways

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....

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Hauptverfasser: Denolly, Solène (VerfasserIn) , Stukalov, Alexey (VerfasserIn) , Barayeu, Uladzimir (VerfasserIn) , Rosinski, Alina N. (VerfasserIn) , Kritsiligkou, Paraskevi (VerfasserIn) , Joecks, Sebastian (VerfasserIn) , Dick, Tobias P. (VerfasserIn) , Pichlmair, Andreas (VerfasserIn) , Bartenschlager, Ralf (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 05 December 2023
In: Nature Communications
Year: 2023, Jahrgang: 14, Pages: 1-20
ISSN:2041-1723
DOI:10.1038/s41467-023-43665-6
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-023-43665-6
Volltext
Verfasserangaben:Solène Denolly, Alexey Stukalov, Uladzimir Barayeu, Alina N. Rosinski, Paraskevi Kritsiligkou, Sebastian Joecks, Tobias P. Dick, Andreas Pichlmair & Ralf Bartenschlager
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 02.08.2024
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-023-43665-6

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