SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology.
SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology.
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DOI：
10.1016/j.chom.2017.01.015
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发表时间：
2017-03-08
影响因子：
30.3
通讯作者：
Sola I
中科院分区：
文献类型：
--
作者：
Morales L;Oliveros JC;Fernandez-Delgado R;tenOever BR;Enjuanes L;Sola I
严重急性呼吸综合征冠状病毒(SARS-CoV)可导致人类致死性疾病，其特征是炎症反应加剧和广泛的肺部病理。为了解决小非编码RNA在SARS-CoV病理学中的相关性，我们对感染小鼠的肺部RNA进行了深度测序，发现了三个18-22个核苷酸的小病毒RNA(SvRNAs)。这三个svRNA分别来自SARS冠状病毒的nsp3(svRNA-nsp3.1和-nsp3.2)和N(svRNA-N)基因组区域。冠状病毒svRNAs的生物发生与RNaseIII、细胞类型和寄主种类无关，但依赖于病毒复制的程度。Antag omir介导的svRNA-N抑制明显减少了体内肺病理和促炎细胞因子的表达。综上所述，这些数据表明svRNAs参与了SARS-CoV的致病过程，并突出了svRNA-N抗原体作为抗病毒药物的潜力。SARS-CoV小病毒RNA(SvRNA)在感染的肺和细胞培养中被发现，SARS-CoV svRNA的生物发生是RNase III，细胞类型和物种无关的svRNA-N通过抑制3‘端非编码区特异性靶序列svRNA-N抑制mRNAs的表达，在体内减轻肺部病理和促炎细胞因子SARS-CoV引起的加重炎症反应，广泛的肺部病理和致死性疾病。Morales等人。鉴定在肺部感染期间表达的SARS冠状病毒编码的小病毒RNA(SvRNAs)。病毒N基因衍生的svRNA(svRNA-N)有助于增强肺部炎症病理。反义svRNA-N抑制剂显著减少了小鼠体内感染期间的肺部炎症。
Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18–22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals. SARS-CoV small viral RNAs (svRNA) were identified in infected lungs and cell culture SARS-CoV svRNAs biogenesis was RNase III, cell type, and species independent svRNA-N repressed the expression of mRNAs with 3′ UTR specific target sequences svRNA-N inhibition in vivo reduced lung pathology and proinflammatory cytokines SARS-CoV causes exacerbated inflammatory responses, extensive lung pathology, and lethal disease in humans. Morales et al. identify SARS-CoV-encoded small viral RNAs (svRNAs) expressed during lung infection. Virus N gene-derived svRNA (svRNA-N) contributes to enhanced lung inflammatory pathology. Antisense svRNA-N inhibitors significantly reduced pulmonary inflammation during in vivo infection in mice.
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DOI：
10.1038/nrmicro2147
发表时间：
2009-06
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.1
作者：
Regla-Nava JA;Jimenez-Guardeño JM;Nieto-Torres JL;Gallagher TM;Enjuanes L;DeDiego ML
通讯作者：
DeDiego ML
影响因子：
5.4
作者：
Page, Carly;Goicochea, Lindsay;Frieman, Matthew
通讯作者：
Frieman, Matthew
影响因子：
7.6
作者：
Báez-Santos YM;St John SE;Mesecar AD
通讯作者：
Mesecar AD
DOI：
10.1016/s0140-6736(03)13413-7
发表时间：
2003-05-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Nicholls JM;Poon LL;Lee KC;Ng WF;Lai ST;Leung CY;Chu CM;Hui PK;Mak KL;Lim W;Yan KW;Chan KH;Tsang NC;Guan Y;Yuen KY;Peiris JS
通讯作者：
Peiris JS