ID: 203
Identifieur interne : 001765 ( Main/Exploration ); précédent : 001764; suivant : 001766ID: 203
Auteurs : Babal K. Jha [États-Unis] ; Joshua M. Thornbrough [États-Unis] ; Stephen A. Goldstein [États-Unis] ; Ruth Elliott [États-Unis] ; Susan R. Weiss [États-Unis] ; Robert H. Silverman [États-Unis]Source :
- Cytokine [ 1043-4666 ] ; 2015.
Abstract
Efficient and productive virus infection often requires viral countermeasures that block innate immunity. The interferon-inducible 2′,5′-oligoadenylate (2-5A) synthetases (OAS) and ribonuclease L (RNase L) are components of a potent host antiviral pathway. We previously showed that murine coronavirus (MHV) accessory protein ns2, group A rotavirus (RVA) VP3 carboxy-terminal domain (VP3-CTD), and mammalian AKAP7 are members of 2H phosphoesterase superfamily with 2′-phosphodiesterase (2′-PDE) activity that potently cleaves 2-5A thereby preventing activation of RNase L (Zhao, Jha et al., PMID:
Url:
DOI: 10.1016/j.cyto.2015.08.207
PubMed: NONE
PubMed Central: 7129261
Affiliations:
Links toward previous steps (curation, corpus...)
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Le document en format XML
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<affiliation wicri:level="2"><nlm:aff id="af005">Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA</nlm:aff>
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<placeName><region type="state">Pennsylvanie</region>
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<author><name sortKey="Goldstein, Stephen A" sort="Goldstein, Stephen A" uniqKey="Goldstein S" first="Stephen A." last="Goldstein">Stephen A. Goldstein</name>
<affiliation wicri:level="2"><nlm:aff id="af010">Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA</nlm:aff>
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<author><name sortKey="Silverman, Robert H" sort="Silverman, Robert H" uniqKey="Silverman R" first="Robert H." last="Silverman">Robert H. Silverman</name>
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<series><title level="j">Cytokine</title>
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<front><div type="abstract" xml:lang="en"><p>Efficient and productive virus infection often requires viral countermeasures that block innate immunity. The interferon-inducible 2′,5′-oligoadenylate (2-5A) synthetases (OAS) and ribonuclease L (RNase L) are components of a potent host antiviral pathway. We previously showed that murine coronavirus (MHV) accessory protein ns2, group A rotavirus (RVA) VP3 carboxy-terminal domain (VP3-CTD), and mammalian AKAP7 are members of 2H phosphoesterase superfamily with 2′-phosphodiesterase (2′-PDE) activity that potently cleaves 2-5A thereby preventing activation of RNase L (Zhao, Jha et al., PMID: <ext-link ext-link-type="uri" xlink:href="pmid:22704621" id="ir005">22704621</ext-link>
; Zhang, Jha et al., PMID: <ext-link ext-link-type="uri" xlink:href="pmid:23878220" id="ir010">23878220</ext-link>
and Gusho, Zhang, Jha et al., PMID: <ext-link ext-link-type="uri" xlink:href="pmid:24987090" id="ir015">24987090</ext-link>
). Here, we will demonstrate that Middle East respiratory syndrome (MERS)-CoV gene NS4b encodes a homologous and similar PDE that cleaves 2-5A in vitro (km/Kcat = 12.1 M<sup>−1</sup>
s<sup>−1</sup>
), inhibits 2-5A accumulation in cell culture and prevents ribosomal (r) RNA degradation in murine bone marrow macrophages (BMM), a hallmark of RNase L antagonism, and rescues an MHV mutant virus with a catalytically inactive NS2a protein unable to antagonize RNase L in vivo. Interestingly, NS4b has a nuclear localization signal however there is a mixed nuclear/cytoplasmic localization when overexpressed in human airway cell line A549 and in BMM when expressed from chimeric MHV. Viral evasion of OAS/RNase L pathway is a critical hepatovirulence determinant for lineage A Betacoronavirus mouse hepatitis virus (MHV). Taken together, our data suggest that RNase L antagonism may be a critical component of MERS-CoV pathogenesis. Additionally, this is the first evidence of RNase L antagonism by a lineage C Betacoronavirus.</p>
</div>
</front>
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<region><li>Ohio</li>
<li>Pennsylvanie</li>
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<tree><country name="États-Unis"><region name="Ohio"><name sortKey="Jha, Babal K" sort="Jha, Babal K" uniqKey="Jha B" first="Babal K." last="Jha">Babal K. Jha</name>
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<name sortKey="Elliott, Ruth" sort="Elliott, Ruth" uniqKey="Elliott R" first="Ruth" last="Elliott">Ruth Elliott</name>
<name sortKey="Goldstein, Stephen A" sort="Goldstein, Stephen A" uniqKey="Goldstein S" first="Stephen A." last="Goldstein">Stephen A. Goldstein</name>
<name sortKey="Silverman, Robert H" sort="Silverman, Robert H" uniqKey="Silverman R" first="Robert H." last="Silverman">Robert H. Silverman</name>
<name sortKey="Thornbrough, Joshua M" sort="Thornbrough, Joshua M" uniqKey="Thornbrough J" first="Joshua M." last="Thornbrough">Joshua M. Thornbrough</name>
<name sortKey="Weiss, Susan R" sort="Weiss, Susan R" uniqKey="Weiss S" first="Susan R." last="Weiss">Susan R. Weiss</name>
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