在感染候选疫苗 DEN4Δ30 的人类细胞中，亚基因组 RNA 的积累减少会增加病毒对 I 型干扰素的敏感性。
Decreased accumulation of subgenomic RNA in human cells infected with vaccine candidate DEN4Δ30 increases viral susceptibility to type I interferon.
机构信息
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Building 31, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, USA.
出版信息
Vaccine. 2018 Jun 7;36(24):3460-3467. doi: 10.1016/j.vaccine.2018.04.087. Epub 2018 May 8.
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.
美国国立卫生研究院（NIH）通过从病毒基因组的非翻译区缺失 30 个核苷酸（Δ30）开发了减毒登革热病毒（DENV）候选疫苗。尽管这种减毒策略已被证明可有效产生安全和免疫原性的疫苗株，但减毒的分子机制在很大程度上仍不清楚。为了研究观察到的减毒表型的介导物，在野生型亲本 DENV 和 DENVΔ30 减毒疫苗候选物之间比较了翻译效率、基因组复制、细胞毒性和 I 型干扰素易感性的差异。我们观察到，感染的人细胞中来自疫苗候选物的亚基因组 RNA（sfRNA）的积累减少导致 I 型干扰素易感性增加，并提出这是 3'UTRΔ30 突变产生的减毒机制之一。
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