SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology

被引：80

作者：

Morales, Lucia ^{[1
]}

Carlos Oliveros, Juan ^{[2
]}

Fernandez-Delgado, Raul ^{[1
]}

tenOever, Benjamin Robert ^{[3
]}

Enjuanes, Luis ^{[1
]}

Sola, Isabel ^{[1
]}

机构：

[1] CSIC, CNB, Dept Mol & Cell Biol, Madrid 28049, Spain

[2] CSIC, CNB, Computat Genom Serv, Madrid 28049, Spain

[3] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

来源：

CELL HOST & MICROBE | 2017年 / 21卷 / 03期

基金：

美国国家卫生研究院;

关键词：

ACUTE RESPIRATORY SYNDROME; SYNDROME CORONAVIRUS; NONCODING RNAS; MICRORNAS; PATHOGENESIS; REPLICATION; MICE; TRANSCRIPTION; INHIBITION; INTERFERON;

D O I：

10.1016/j.chom.2017.01.015

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 SARSCoV 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.

引用

页码：344 / 355

页数：12

共 39 条

[11] Inhibition of NF-κB-Mediated Inflammation in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice Increases Survival [J].

DeDiego, Marta L. ;

Nieto-Torres, Jose L. ;

Regla-Nava, Jose A. ;

Jimenez-Guardeno, Jose M. ;

Fernandez-Delgado, Raul ;

Fett, Craig ;

Castano-Rodriguez, Carlos ;

Perlman, Stanley ;

Enjuanes, Luis .

JOURNAL OF VIROLOGY, 2014, 88 (02) :913-924

[12] Antiviral immunity directed by small RNAs [J].

Ding, Shou-Wei ;

Voinnet, Olivier .

CELL, 2007, 130 (03) :413-426

[13]

Enjuanes L., 2008, Encyclopedia of Virology, P419

[14] Most mammalian mRNAs are conserved targets of microRNAs [J].

Friedman, Robin C. ;

Farh, Kyle Kai-How ;

Burge, Christopher B. ;

Bartel, David P. .

GENOME RESEARCH, 2009, 19 (01) :92-105

[15] Virus-encoded microRNAs [J].

Grundhoff, Adam ;

Sullivan, Christopher S. .

VIROLOGY, 2011, 411 (02) :325-343

[16] Treatment of HCV Infection by Targeting MicroRNA [J].

Janssen, Harry L. A. ;

Reesink, Hendrik W. ;

Lawitz, Eric J. ;

Zeuzem, Stefan ;

Rodriguez-Torres, Maribel ;

Patel, Keyur ;

van der Meer, Adriaan J. ;

Patick, Amy K. ;

Chen, Alice ;

Zhou, Yi ;

Persson, Robert ;

King, Barney D. ;

Kauppinen, Sakari ;

Levin, Arthur A. ;

Hodges, Michael R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (18) :1685-1694

[17] The PDZ-Binding Motif of Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Is a Determinant of Viral Pathogenesis [J].

Jimenez-Guardeno, Jose M. ;

Nieto-Torres, Jose L. ;

DeDiego, Marta L. ;

Regla-Nava, Jose A. ;

Fernandez-Delgado, Raul ;

Castano-Rodriguez, Carlos ;

Enjuanes, Luis .

PLOS PATHOGENS, 2014, 10 (08)

[18] Proteomics analysis unravels the functional repertoire of coronavirus nonstructural protein 3 [J].

Neuman, Benjamin W. ;

Joseph, Jeremiah S. ;

Saikatendu, Kumar S. ;

Serrano, Pedro ;

Chatterjee, Amarnath ;

Johnson, Margaret A. ;

Liao, Lujian ;

Klaus, Joseph P. ;

Yates, John R., III ;

Wuethrich, Kurt ;

Stevens, Raymond C. ;

Buchmeier, Michael J. ;

Kuhn, Peter .

JOURNAL OF VIROLOGY, 2008, 82 (11) :5279-5294

[19] Lung pathology of fatal severe acute respiratory syndrome [J].

Nicholls, JM ;

Poon, LLM ;

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, JSM .

LANCET, 2003, 361 (9371) :1773-1778

[20] Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis [J].

Nieto-Torres, Jose L. ;

DeDiego, Marta L. ;

Verdia-Baguena, Carmina ;

Jimenez-Guardeno, Jose M. ;

Regla-Nava, Jose A. ;

Fernandez-Delgado, Raul ;

Castano-Rodriguez, Carlos ;

Alcaraz, Antonio ;

Torres, Jaume ;

Aguilella, Vicente M. ;

Enjuanes, Luis .

PLOS PATHOGENS, 2014, 10 (05)

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