دورية أكاديمية
Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response.
| العنوان: | Bat Severe Acute Respiratory Syndrome-Like Coronavirus WIV1 Encodes an Extra Accessory Protein, ORFX, Involved in Modulation of the Host Immune Response. |
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| المؤلفون: | Zeng LP; Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China., Gao YT; Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China., Ge XY; Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China., Zhang Q; Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China., Peng C; Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China., Yang XL; Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China., Tan B; Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China., Chen J; Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China., Chmura AA; EcoHealth Alliance, New York, New York, USA., Daszak P; EcoHealth Alliance, New York, New York, USA., Shi ZL; Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China zlshi@wh.iov.cn. |
| المصدر: | Journal of virology [J Virol] 2016 Jun 24; Vol. 90 (14), pp. 6573-6582. Date of Electronic Publication: 2016 Jun 24 (Print Publication: 2016). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Society For Microbiology Original Publication: Baltimore, American Society for Microbiology. |
| مواضيع طبية MeSH: | Chiroptera/*virology , Open Reading Frames/*immunology , Severe acute respiratory syndrome-related coronavirus/*immunology , Severe Acute Respiratory Syndrome/*immunology , Virus Replication/*immunology, Animals ; Antiviral Agents/pharmacology ; Chlorocebus aethiops ; HeLa Cells ; Humans ; Interferon-beta/pharmacology ; NF-kappa B/metabolism ; Open Reading Frames/genetics ; Severe Acute Respiratory Syndrome/drug therapy ; Severe Acute Respiratory Syndrome/virology ; Vero Cells |
| مستخلص: | Unlabelled: Bats harbor severe acute respiratory syndrome (SARS)-like coronaviruses (SL-CoVs) from which the causative agent of the 2002-2003 SARS pandemic is thought to have originated. However, despite the fact that a large number of genetically diverse SL-CoV sequences have been detected in bats, only two strains (named WIV1 and WIV16) have been successfully cultured in vitro These two strains differ from SARS-CoV only in containing an extra open reading frame (ORF) (named ORFX), between ORF6 and ORF7, which has no homology to any known protein sequences. In this study, we constructed a full-length cDNA clone of SL-CoV WIV1 (rWIV1), an ORFX deletion mutant (rWIV1-ΔX), and a green fluorescent protein (GFP)-expressing mutant (rWIV1-GFP-ΔX). Northern blotting and fluorescence microscopy indicate that ORFX was expressed during WIV1 infection. A virus infection assay showed that rWIV1-ΔX replicated as efficiently as rWIV1 in Vero E6, Calu-3, and HeLa-hACE2 cells. Further study showed that ORFX could inhibit interferon production and activate NF-κB. Our results demonstrate for the first time that the unique ORFX in the WIV1 strain is a functional gene involving modulation of the host immune response but is not essential for in vitro viral replication. Importance: Bats harbor genetically diverse SARS-like coronaviruses (SL-CoVs), and some of them have the potential for interspecies transmission. A unique open reading frame (ORFX) was identified in the genomes of two recently isolated bat SL-CoV strains (WIV1 and -16). It will therefore be critical to clarify whether and how this protein contributes to virulence during viral infection. Here we revealed that the unique ORFX is a functional gene that is involved in the modulation of the host immune response but is not essential for in vitro viral replication. Our results provide important information for further exploration of the ORFX function in the future. Moreover, the reverse genetics system we constructed will be helpful for study of the pathogenesis of this group of viruses and to develop therapeutics for future control of emerging SARS-like infections. (Copyright © 2016, American Society for Microbiology. All Rights Reserved.) |
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| معلومات مُعتمدة: | R01 AI110964 United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Antiviral Agents) 0 (NF-kappa B) 77238-31-4 (Interferon-beta) |
| تواريخ الأحداث: | Date Created: 20160513 Date Completed: 20170518 Latest Revision: 20221207 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC4936131 |
| DOI: | 10.1128/JVI.03079-15 |
| PMID: | 27170748 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5514 |
|---|---|
| DOI: | 10.1128/JVI.03079-15 |