Efficient Dicer processing of virus-derived double-stranded RNAs and its modulation by RIG-I-like receptor LGP2.
Efficient Dicer processing of virus-derived double-stranded RNAs and its modulation by RIG-I-like receptor LGP2.
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病毒源性双链 RNA 的高效 Dicer 加工及其 RIG-I 样受体 LGP2 的调节
DOI：
10.1371/journal.ppat.1009790
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发表时间：
2021-08
期刊：
影响因子：
6.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Zhang Y;Xu Y;Dai Y;Li Z;Wang J;Ye Z;Ren Y;Wang H;Li WX;Lu J;Ding SW;Li Y
干扰素调节的抗病毒反应对于诱导哺乳动物先天性和适应性免疫至关重要。生产病毒衍生的小干扰RNA (vsiRNA)，通过RNA干扰(RNAi)来限制病毒感染，是最近发现的哺乳动物对几种RNA病毒的免疫反应，这些病毒会导致流感和寨卡病毒等重要的人类疾病。然而，人们对哺乳动物体细胞中病毒双链 RNA 复制中间体 (dsRNA-vRIs) 的 Dicer 加工知之甚少。在这里，我们表明，当两者都是由人 Dicer 从头表达时产生的，受感染的体细胞比细胞 microRNA 产生更多的流感 vsiRNA，这表明 dsRNA-vRI 并不是先前根据合成长 dsRNA 的体外 Dicer 加工提出的较差的 Dicer 底物。我们报告了野生型野田村病毒感染过程中规范 vsiRNA 产生及其 RNAi 抑制蛋白 B2 在两种乳鼠品系中直接隔离 vsiRNA 的第一个证据。此外，感染触发的 SINV 靶向 vsiRNA 的先前产生减少了辛德比斯病毒 (SINV) 体内积累，并通过 SINV 基因组中顺式 B2 的异源表达增加了体内积累，表明诱导的 RNAi 反应具有抗病毒功能。这些发现表明，与人工长 dsRNA 不同，在成熟体细胞的真实感染过程中产生的 dsRNA-vRI 可以被 Dicer 有效加工成 vsiRNA，以指导抗病毒 RNAi。有趣的是，将 dsRNA-vRI 加工成 vsiRNA 的过程受到 LGP2（遗传学和生理学实验室 2）的抑制，LGP2 由干扰素刺激基因 (ISG) 编码，最近显示可抑制细胞培养物中人工长 dsRNA 的 Dicer 加工。因此，我们的工作进一步表明干扰素反应中已知的 ISG 对抗病毒 RNAi 进行负调节。
The interferon-regulated antiviral responses are essential for the induction of both innate and adaptive immunity in mammals. Production of virus-derived small-interfering RNAs (vsiRNAs) to restrict virus infection by RNA interference (RNAi) is a recently identified mammalian immune response to several RNA viruses, which cause important human diseases such as influenza and Zika virus. However, little is known about Dicer processing of viral double-stranded RNA replicative intermediates (dsRNA-vRIs) in mammalian somatic cells. Here we show that infected somatic cells produced more influenza vsiRNAs than cellular microRNAs when both were produced by human Dicer expressed de novo, indicating that dsRNA-vRIs are not poor Dicer substrates as previously proposed according to in vitro Dicer processing of synthetic long dsRNA. We report the first evidence both for canonical vsiRNA production during wild-type Nodamura virus infection and direct vsiRNA sequestration by its RNAi suppressor protein B2 in two strains of suckling mice. Moreover, Sindbis virus (SINV) accumulation in vivo was decreased by prior production of SINV-targeting vsiRNAs triggered by infection and increased by heterologous expression of B2 in cis from SINV genome, indicating an antiviral function for the induced RNAi response. These findings reveal that unlike artificial long dsRNA, dsRNA-vRIs made during authentic infection of mature somatic cells are efficiently processed by Dicer into vsiRNAs to direct antiviral RNAi. Interestingly, Dicer processing of dsRNA-vRIs into vsiRNAs was inhibited by LGP2 (laboratory of genetics and physiology 2), which was encoded by an interferon-stimulated gene (ISG) shown recently to inhibit Dicer processing of artificial long dsRNA in cell culture. Our work thus further suggests negative modulation of antiviral RNAi by a known ISG from the interferon response.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
6.4
作者：
Girardi E;Chane-Woon-Ming B;Messmer M;Kaukinen P;Pfeffer S
通讯作者：
Pfeffer S
DOI：
10.1073/pnas.1921861117
发表时间：
2020-07-07
影响因子：
11.1
作者：
Esser-Nobis, Katharina;Hatfield, Lauren D.;Gale, Michael, Jr.
通讯作者：
Gale, Michael, Jr.
影响因子：
7
作者：
Ding SW;Han Q;Wang J;Li WX
通讯作者：
Li WX
影响因子：
30.3
作者：
Aliyari, Roghiyh;Wu, Qingfa;Li, Hong-Wei;Wang, Xiao-Hong;Li, Feng;Green, Lance D.;Han, Cliff S.;Li, Wan-Xiang;Ding, Shou-Wei
通讯作者：
Ding, Shou-Wei