Decreased accumulation of subgenomic RNA in human cells infected with vaccine candidate DEN4Δ30 increases viral susceptibility to type I interferon

Vaccine
José Bustos-ArriagaStephen S Whitehead

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.

Citations

Apr 8, 2020·Frontiers in Cellular and Infection Microbiology·Kaihao FengJing An
Sep 15, 2018·Pathogens and Global Health·Sandra BosPhilippe Despres
Nov 30, 2019·Reviews in Medical Virology·Zhong-Yu Liu, Cheng-Feng Qin
Nov 7, 2019·Viral Immunology·Branden R NelsonKristina M Adams Waldorf
Oct 19, 2020·Current Opinion in Microbiology·Shwetha Shivaprasad, Peter Sarnow
May 1, 2021·Life·Kevin Nicolas CalderonClara Isabel Bermudez-Santana
Dec 1, 2021·The Journal of General Virology·Tanamas SiriphanitchakornMilly M Choy

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