Updated project metadata.
Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor vaccine are available. ZIKV is an enveloped RNA virus, replicating in the cytoplasm in close association with ER membranes with the help of host cell factors that are poorly characterized. Here, we isolated ER membranes from ZIKV-infected cells and determined their proteome. 46 host cell factors were enriched in ZIKV remodeled membranes, several of these proteins having a role in redox pathways. 4 proteins were 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 promoting stability of non-structural proteins having transmembrane domains; Adenosylhomocysteinase (AHCY) promoting m6A methylation of ZIKV RNA and thus immune evasion. These results highlight the involvement of redox enzymes in ZIKV life cycle and their recruitment to virally remodeled ER membranes.