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

Author

Listed:
  • Solène Denolly

    (Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research)

  • Alexey Stukalov

    (Technical University of Munich, School of Medicine, Institute of Virology)

  • Uladzimir Barayeu

    (DKFZ-ZMBH Alliance
    Faculty of Biosciences, Heidelberg University)

  • Alina N. Rosinski

    (Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research)

  • Paraskevi Kritsiligkou

    (DKFZ-ZMBH Alliance)

  • Sebastian Joecks

    (Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research)

  • Tobias P. Dick

    (DKFZ-ZMBH Alliance
    Faculty of Biosciences, Heidelberg University)

  • Andreas Pichlmair

    (Technical University of Munich, School of Medicine, Institute of Virology
    Munich Partner Site)

  • Ralf Bartenschlager

    (Heidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Disease Research
    German Cancer Research Center (DKFZ))

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.

Suggested Citation

  • Solène Denolly & Alexey Stukalov & Uladzimir Barayeu & Alina N. Rosinski & Paraskevi Kritsiligkou & Sebastian Joecks & Tobias P. Dick & Andreas Pichlmair & Ralf Bartenschlager, 2023. "Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43665-6
    DOI: 10.1038/s41467-023-43665-6
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    Cited by:

    1. Rafael T. Michita & Long B. Tran & Steven J. Bark & Deepak Kumar & Shay A. Toner & Joyce Jose & Indira U. Mysorekar & Anoop Narayanan, 2025. "Zika virus NS1 drives tunneling nanotube formation for mitochondrial transfer and stealth transmission in trophoblasts," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    2. Linliang Zhang & Hongyun Wang & Chao Han & Qi Dong & Jie Yan & Weiwei Guo & Chao Shan & Wen Zhao & Pu Chen & Rui Huang & Ying Wu & Yu Chen & Yali Qin & Mingzhou Chen, 2024. "AMFR-mediated Flavivirus NS2A ubiquitination subverts ER-phagy to augment viral pathogenicity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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