The Internal Ribosome Entry Site of Dengue Virus mRNA Is Active When Cap-Dependent Translation Initiation Is Inhibited

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dc.contributor.authorFernandez-Garcia, Leandro
dc.contributor.authorAngulo, Jenniffer
dc.contributor.authorRamos, Hade
dc.contributor.authorBarrera, Aldo
dc.contributor.authorPino, Karla
dc.contributor.authorVera-Otarola, Jorge
dc.contributor.authorLopez-Lastra, Marcelo
dc.date.accessioned2025-01-20T23:53:35Z
dc.date.available2025-01-20T23:53:35Z
dc.date.issued2021
dc.description.abstractDengue virus (DENV) is an enveloped, positive-sense, single-stranded RNA virus belonging to the Flaviviridae family. Translation initiation of DENV mRNA can occur by a cap-dependent or a cap-independent mechanism. Two non-mutually exclusive cap-independent mechanisms of translation initiation have been described for DENV mRNA. The first corresponds to a 5'-end-dependent, internal ribosome entry site (IRES)-independent mechanism, while the second relies on IRES-dependent initiation. In this report, we study the recently discovered DENV IRES. The results show that the DENV IRES is functional in the rabbit reticulocyte lysate (RRL). In accordance, the activity of the DENV IRES was resistant to the cleavage of eukaryotic initiation factor 4G (eIF4G) by the Foot-and-mouth disease virus leader protease in RRL In cells, the DENV IRES exhibited only marginal activity under standard culture conditions. The DENV IRES showed weak activity in HEK 293T cells; however, DEW IRES activity was significantly enhanced in HEK 293T cells expressing Human rhinovirus 2A protease. These findings suggest that the DENV IRES enables viral protein synthesis under conditions that suppress canonical translation initiation.
dc.description.abstractIMPORTANCE Dengue virus (DENV), the etiological agent of dengue, a febrile and hemorrhagic disease, infects millions of people per year in tropical and subtropical countries. When infecting cells, DENV induces stress conditions known to inhibit canonical protein synthesis. Under these conditions, DENV mRNA thrives using noncanonical modes of translation initiation. In this study, we characterize the mechanism dependent on an internal ribosome entry site (IRES). Here, we describe the activity of the DENV IRES in vitro and cells. We show that in cells, the DENV IRES enables the viral mRNA to translate under conditions that suppress canonical translation initiation.
dc.fuente.origenWOS
dc.identifier.doi10.1128/JVI.01998-20
dc.identifier.eissn1098-5514
dc.identifier.issn0022-538X
dc.identifier.urihttps://doi.org/10.1128/JVI.01998-20
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94978
dc.identifier.wosidWOS:000619748400003
dc.issue.numero5
dc.language.isoen
dc.revistaJournal of virology
dc.rightsacceso restringido
dc.subjectdengue fever
dc.subjectinternal ribosome entry site
dc.subjecttranslation initiation
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe Internal Ribosome Entry Site of Dengue Virus mRNA Is Active When Cap-Dependent Translation Initiation Is Inhibited
dc.typeartículo
dc.volumen95
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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