Defective Interfering Genomes and the Full-Length Viral Genome Trigger RIG-I After Infection With Vesicular Stomatitis Virus in a Replication Dependent Manner.

Defective Interfering Genomes and the Full-Length Viral Genome Trigger RIG-I After Infection With Vesicular Stomatitis Virus in a Replication Dependent Manner.
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DOI:
10.3389/fimmu.2021.595390
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发表时间:
2021
影响因子:
7.3
通讯作者:
Rothenfusser S
Rothenfusser S
中科院分区:
医学2区
文献类型:
--
作者:
Linder A;Bothe V;Linder N;Schwarzlmueller P;Dahlström F;Bartenhagen C;Dugas M;Pandey D;Thorn-Seshold J;Boehmer DFR;Koenig LM;Kobold S;Schnurr M;Raedler J;Spielmann G;Karimzadeh H;Schmidt A;Endres S;Rothenfusser S

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具有复制能力的水疱性口炎病毒(VSV)是埃博拉疫苗的基础,VSV株是作为溶瘤病毒而开发的。这两种功能都依赖于Vsv诱导足够量的干扰素-α/β的能力。因此,了解VSV如何触发干扰素反应是很重要的。VSV通过维甲酸诱导基因I(RIG-I)激活先天免疫,RIG-I是病毒RNA的传感器。我们的结果表明,VSV需要复制才能产生强大的干扰素反应。对RIG-I相关RNA的分析发现,复制回缺陷干扰(DI)基因组和全长病毒基因组是RIG-I的主要触发因素。耗尽DI基因组的VSV库存失去了大部分干扰素刺激活性。然而,剩下的全长基因组和Leader-N-Read-Thry序列仍然触发了RIG-I。意识到DI基因组是先天免疫反应的触发者,这将有助于标准化DI基因组内容,并有目的地耗尽或使用DI基因组作为基于VSV的治疗的天然佐剂。
Replication competent vesicular stomatitis virus (VSV) is the basis of a vaccine against Ebola and VSV strains are developed as oncolytic viruses. Both functions depend on the ability of VSV to induce adequate amounts of interferon-α/β. It is therefore important to understand how VSV triggers interferon responses. VSV activates innate immunity via retinoic acid-inducible gene I (RIG-I), a sensor for viral RNA. Our results show that VSV needs to replicate for a robust interferon response. Analysis of RIG-I-associated RNA identified a copy-back defective-interfering (DI) genome and full-length viral genomes as main trigger of RIG-I. VSV stocks depleted of DI genomes lost most of their interferon-stimulating activity. The remaining full-length genome and leader-N-read-through sequences, however, still triggered RIG-I. Awareness for DI genomes as trigger of innate immune responses will help to standardize DI genome content and to purposefully deplete or use DI genomes as natural adjuvants in VSV-based therapeutics.
通过RIG-I介导的5'-二磷酸RNA识别的抗病毒药免疫。
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