Decreased accumulation of subgenomic RNA in human cells infected with vaccine candidate DEN4Δ30 increases viral susceptibility to type I interferon. Issue 24 (7th June 2018)

• Record Type: Journal Article
• Authors: Bustos-Arriaga, José; Gromowski, Gregory D.; Tsetsarkin, Konstantin A.; Firestone, Cai-Yen; Castro-Jiménez, Tannya; Pletnev, Alexander G.; Cedillo-Barrón, Leticia; Whitehead, Stephen S.
• Is Part Of: Vaccine. Volume 36:Issue 24(2018)
• Page Start: 3460
• Page End: 3467
• Publication Date: 2018-06-07
• Subjects: Dengue -- sfRNA -- Innate immunity -- Vaccine candidate; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.04.087
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: The NIH has developed live attenuated dengue virus (DENV) vaccine candidates by deletion of 30 nucleotides (Δ30) from the untranslated region of the viral genome. Although this attenuation strategy has proven to be effective in generating safe and immunogenic vaccine strains, the molecular mechanism of attenuation is largely unknown. To examine the mediators of the observed attenuation phenotype, differences in translation efficiency, genome replication, cytotoxicity, and type I interferon susceptibility were compared between wild type parental DENV and DENVΔ30 attenuated vaccine candidates. We observed that decreased accumulation of subgenomic RNA (sfRNA) from the vaccine candidates in infected human cells causes increased type I IFN susceptibility and propose this as one of the of attenuation mechanisms produced by the 3′ UTR Δ30 mutation.