Human DDX3X unwinds Japanese encephalitis and Zika viral 5' terminal regions

dc.contributor.authorNelson, Corey R.
dc.contributor.authorMrozowich, Tyler
dc.contributor.authorGemmill, Darren L.
dc.contributor.authorPark, Sean M.
dc.contributor.authorPatel, Trushar R.
dc.date.accessioned2022-12-21T17:14:46Z
dc.date.available2022-12-21T17:14:46Z
dc.date.issued2021
dc.descriptionOpen access article. Creative Commons Attribution 4.0 International License (CC BY 4.0) appliesen_US
dc.description.abstractFlavivirus genus includes many deadly viruses such as the Japanese encephalitis virus (JEV) and Zika virus (ZIKV). The 5′ terminal regions (TR) of flaviviruses interact with human proteins and such interactions are critical for viral replication. One of the human proteins identified to interact with the 5′ TR of JEV is the DEAD-box helicase, DDX3X. In this study, we in vitro transcribed the 5′ TR of JEV and demonstrated its direct interaction with recombinant DDX3X (Kd of 1.66 ± 0.21 µM) using microscale thermophoresis (MST). Due to the proposed structural similarities of 5′ and 3′ TRs of flaviviruses, we investigated if the ZIKV 5′ TR could also interact with human DDX3X. Our MST studies suggested that DDX3X recognizes ZIKV 5′ TR with a Kd of 7.05 ± 0.75 µM. Next, we performed helicase assays that suggested that the binding of DDX3X leads to the unwinding of JEV and ZIKV 5′ TRs. Overall, our data indicate, for the first time, that DDX3X can directly bind and unwind in vitro transcribed flaviviral TRs. In summary, our work indicates that DDX3X could be further explored as a therapeutic target to inhibit Flaviviral replicationen_US
dc.identifier.citationNelson, C., Mrozowich, T., Gemmill, D. L., Park, S. M., & Patel, T. R. (2021). Human DDX3X unwinds Japanese encephalitis and Zika viral 5' terminal regions. International Journal of Molecular Sciences, 22(1), 413. https://doi.org/10.3390/ijms22010413en_US
dc.identifier.urihttps://hdl.handle.net/10133/6397
dc.language.isoen_CAen_US
dc.publisherMDPIen_US
dc.publisher.departmentDepartment of Chemistry & Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.institutionUniversity of Calgary
dc.publisher.institutionUniversity of Alberta
dc.publisher.urlhttps://doi.org/10.3390/ijms22010413
dc.subjectDDX3Xen_US
dc.subjectJapanese encephalitis virusen_US
dc.subjectViral terminal regionsen_US
dc.subjectHost-viral interactionsen_US
dc.subjectIn vitro transcriptionen_US
dc.subjectMicroscale thermophoresisen_US
dc.subjectRNA helicase assaysen_US
dc.subject.lcshJapanese B. encephalitis
dc.subject.lcshZika virus
dc.subject.lcshHost-virus relationships
dc.subject.lcshFlaviviruses
dc.titleHuman DDX3X unwinds Japanese encephalitis and Zika viral 5' terminal regionsen_US
dc.typeArticleen_US
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