AI Summary
Researchers have identified host cell factors that are involved in the Zika virus life cycle and are enriched in the virus-infected ER membranes. These factors play roles in redox and methylation pathways, and their accumulation at the ER membranes contributes to the virus's replication and assembly. This study provides insights into potential targets for antiviral treatments.
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.
Zika virus (ZIKV), a mosquito-borne flavivirus belonging to the Flaviviridae family, was first isolated from an infected captive, sentinel rhesus monkey in the Zika forest in Uganda<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 1" title="Dick, G. W. & Haddow, A. J. Uganda S virus; a hitherto unrecorded virus isolated from mosquitoes in Uganda. I.