Activation of the Antiviral Kinase PKR and Viral Countermeasures
Identifieur interne : 000808 ( Pmc/Curation ); précédent : 000807; suivant : 000809Activation of the Antiviral Kinase PKR and Viral Countermeasures
Auteurs : Bianca Dauber [Canada] ; Thorsten Wolff [Allemagne]Source :
- Viruses [ 1999-4915 ] ; 2009.
Abstract
The interferon-induced double-stranded (ds)RNA-dependent protein kinase (PKR) limits viral replication by an eIF2α-mediated block of translation. Although many negative-strand RNA viruses activate PKR, the responsible RNAs have long remained elusive, as dsRNA, the canonical activator of PKR, has not been detected in cells infected with such viruses. In this review we focus on the activating RNA molecules of different virus families, in particular the negative-strand RNA viruses. We discuss the recently identified non-canonical activators 5′-triphosphate RNA and the vRNP of influenza virus and give an update on strategies of selected RNA and DNA viruses to prevent activation of PKR.
Url:
DOI: 10.3390/v1030523
PubMed: 21994559
PubMed Central: 3185532
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Activation of the Antiviral Kinase PKR and Viral Countermeasures</title><author><name sortKey="Dauber, Bianca" sort="Dauber, Bianca" uniqKey="Dauber B" first="Bianca" last="Dauber">Bianca Dauber</name><affiliation wicri:level="1"><nlm:aff id="af1-viruses-01-00523"> Department of Medical Microbiology & Immunology, University of Alberta, 632 Heritage Medical Research Center, Edmonton, AB, T6G 2S2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Medical Microbiology & Immunology, University of Alberta, 632 Heritage Medical Research Center, Edmonton, AB, T6G 2S2</wicri:regionArea></affiliation></author><author><name sortKey="Wolff, Thorsten" sort="Wolff, Thorsten" uniqKey="Wolff T" first="Thorsten" last="Wolff">Thorsten Wolff</name><affiliation wicri:level="1"><nlm:aff id="af2-viruses-01-00523"> P15, Robert Koch-Institute/Nordufer 20, 13353 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea> P15, Robert Koch-Institute/Nordufer 20, 13353 Berlin</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21994559</idno><idno type="pmc">3185532</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185532</idno><idno type="RBID">PMC:3185532</idno><idno type="doi">10.3390/v1030523</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000808</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000808</idno><idno type="wicri:Area/Pmc/Curation">000808</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000808</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Activation of the Antiviral Kinase PKR and Viral Countermeasures</title><author><name sortKey="Dauber, Bianca" sort="Dauber, Bianca" uniqKey="Dauber B" first="Bianca" last="Dauber">Bianca Dauber</name><affiliation wicri:level="1"><nlm:aff id="af1-viruses-01-00523"> Department of Medical Microbiology & Immunology, University of Alberta, 632 Heritage Medical Research Center, Edmonton, AB, T6G 2S2, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea> Department of Medical Microbiology & Immunology, University of Alberta, 632 Heritage Medical Research Center, Edmonton, AB, T6G 2S2</wicri:regionArea></affiliation></author><author><name sortKey="Wolff, Thorsten" sort="Wolff, Thorsten" uniqKey="Wolff T" first="Thorsten" last="Wolff">Thorsten Wolff</name><affiliation wicri:level="1"><nlm:aff id="af2-viruses-01-00523"> P15, Robert Koch-Institute/Nordufer 20, 13353 Berlin, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea> P15, Robert Koch-Institute/Nordufer 20, 13353 Berlin</wicri:regionArea></affiliation></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The interferon-induced double-stranded (ds)RNA-dependent protein kinase (PKR) limits viral replication by an eIF2α-mediated block of translation. Although many negative-strand RNA viruses activate PKR, the responsible RNAs have long remained elusive, as dsRNA, the canonical activator of PKR, has not been detected in cells infected with such viruses. In this review we focus on the activating RNA molecules of different virus families, in particular the negative-strand RNA viruses. We discuss the recently identified non-canonical activators 5′-triphosphate RNA and the vRNP of influenza virus and give an update on strategies of selected RNA and DNA viruses to prevent activation of PKR.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Garcia Sastre, A" uniqKey="Garcia Sastre A">A Garcia-Sastre</name></author><author><name sortKey="Biron, Ca" uniqKey="Biron C">CA Biron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sadler, Aj" uniqKey="Sadler A">AJ Sadler</name></author><author><name sortKey="Williams, Br" uniqKey="Williams B">BR Williams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haines, Gk" uniqKey="Haines G">GK Haines</name></author><author><name sortKey="Panos, Rj" uniqKey="Panos R">RJ Panos</name></author><author><name sortKey="Bak, Pm" uniqKey="Bak P">PM Bak</name></author><author><name sortKey="Brown, T" uniqKey="Brown T">T 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Viruses</journal-id><journal-title-group><journal-title>Viruses</journal-title></journal-title-group><issn pub-type="epub">1999-4915</issn><publisher><publisher-name>Molecular Diversity Preservation International (MDPI)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21994559</article-id><article-id pub-id-type="pmc">3185532</article-id><article-id pub-id-type="doi">10.3390/v1030523</article-id><article-id pub-id-type="publisher-id">viruses-01-00523</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Activation of the Antiviral Kinase PKR and Viral Countermeasures</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Dauber</surname><given-names>Bianca</given-names></name><xref ref-type="aff" rid="af1-viruses-01-00523"><sup>1</sup></xref><xref ref-type="corresp" rid="c1-viruses-01-00523"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wolff</surname><given-names>Thorsten</given-names></name><xref ref-type="aff" rid="af2-viruses-01-00523"><sup>2</sup></xref><xref ref-type="corresp" rid="c1-viruses-01-00523"><sup>*</sup></xref></contrib></contrib-group><aff id="af1-viruses-01-00523"><label>1</label> Department of Medical Microbiology & Immunology, University of Alberta, 632 Heritage Medical Research Center, Edmonton, AB, T6G 2S2, Canada</aff><aff id="af2-viruses-01-00523"><label>2</label> P15, Robert Koch-Institute/Nordufer 20, 13353 Berlin, Germany</aff><author-notes><corresp id="c1-viruses-01-00523"><label>*</label>Authors to whom correspondence should be addressed; E-Mails: <email>Bianca.Dauber@ualberta.ca</email> (B.D.); <email>Wolfft@rki.de</email> (T.W.).</corresp></author-notes><pub-date pub-type="collection"><month>12</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>27</day><month>10</month><year>2009</year></pub-date><volume>1</volume><issue>3</issue><fpage>523</fpage><lpage>544</lpage><history><date date-type="received"><day>11</day><month>8</month><year>2009</year></date><date date-type="rev-recd"><day>26</day><month>10</month><year>2009</year></date><date date-type="accepted"><day>26</day><month>10</month><year>2009</year></date></history><permissions><copyright-statement>© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.</copyright-statement><copyright-year>2009</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>).</license-p></license></permissions><abstract><p>The interferon-induced double-stranded (ds)RNA-dependent protein kinase (PKR) limits viral replication by an eIF2α-mediated block of translation. Although many negative-strand RNA viruses activate PKR, the responsible RNAs have long remained elusive, as dsRNA, the canonical activator of PKR, has not been detected in cells infected with such viruses. In this review we focus on the activating RNA molecules of different virus families, in particular the negative-strand RNA viruses. We discuss the recently identified non-canonical activators 5′-triphosphate RNA and the vRNP of influenza virus and give an update on strategies of selected RNA and DNA viruses to prevent activation of PKR.</p></abstract><kwd-group><kwd>PKR</kwd><kwd>virus</kwd><kwd>dsRNA</kwd><kwd>innate immunity</kwd><kwd>immune evasion</kwd></kwd-group></article-meta></front><floats-group><fig id="f1-viruses-01-00523" position="float"><label>Figure 1.</label><caption><p>Activation of PKR by different viral and synthetic RNAs. Latent PKR binds to (1) perfect dsRNA of viral or synthetic origin, (2) synthetic structured RNA with single stranded tails and a 5′triphosphate, (3) HIV-1 TAR RNA or (4) (possibly incomplete) influenza virus vRNP. This leads to dimerization and autophosphorylation of PKR. Active PKR then phosphorylates its substrate eIF2α, which results in a block of translation. PKR consists of two dsRNA-binding motifs (dsRBM1 + dsRBM2 in light green) and the <italic>N</italic>-terminal and <italic>C</italic>-terminal lobe of the kinase domain (dark green).</p></caption><graphic xlink:href="viruses-01-00523f1"></graphic></fig><table-wrap id="t1-viruses-01-00523" position="float"><label>Table 1.</label><caption><p>Viral RNA structures that potentially activate PKR.</p></caption><table frame="box" rules="all"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1"><bold>Virus (genome)</bold></th><th align="left" valign="top" rowspan="1" colspan="1"><bold>dsRNA detected in IFA</bold></th><th align="left" valign="top" rowspan="1" colspan="1"><bold>Origin of PKR activating RNA</bold></th><th align="left" valign="top" rowspan="1" colspan="1"><bold>Reference</bold></th></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">VacV, AdV, HSV-1, HCMV, MCMV (DNA)</td><td align="left" valign="top" rowspan="1" colspan="1">+</td><td align="left" valign="top" rowspan="1" colspan="1">overlapping converging transcription</td><td align="left" valign="top" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b36-viruses-01-00523">36</xref>–<xref ref-type="bibr" rid="b41-viruses-01-00523">41</xref>]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">HIV-1 (RNA/DNA)</td><td align="left" valign="top" rowspan="1" colspan="1">n. a.</td><td align="left" valign="top" rowspan="1" colspan="1">TAR RNA/possibly as dimer</td><td align="left" valign="top" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b52-viruses-01-00523">52</xref>–<xref ref-type="bibr" rid="b54-viruses-01-00523">54</xref>,<xref ref-type="bibr" rid="b56-viruses-01-00523">56</xref>]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">ReoV (dsRNA)</td><td align="left" valign="top" rowspan="1" colspan="1">+</td><td align="left" valign="top" rowspan="1" colspan="1">dsRNA genome</td><td align="left" valign="top" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b39-viruses-01-00523">39</xref>,<xref ref-type="bibr" rid="b42-viruses-01-00523">42</xref>,<xref ref-type="bibr" rid="b49-viruses-01-00523">49</xref>]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Rubella V., SFV, SINV, SARS CoV, EMCV, Kunjin V., PolioV, TBEV, HCV, DENV. (+ssRNA)</td><td align="left" valign="top" rowspan="1" colspan="1">+</td><td align="left" valign="top" rowspan="1" colspan="1">replication intermediates or base-paired secondary structure elements</td><td align="left" valign="top" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b39-viruses-01-00523">39</xref>,<xref ref-type="bibr" rid="b43-viruses-01-00523">43</xref>–<xref ref-type="bibr" rid="b48-viruses-01-00523">48</xref>]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Influenza V. (-ssRNA, segm.)</td><td align="left" valign="top" rowspan="1" colspan="1">–</td><td align="left" valign="top" rowspan="1" colspan="1">vRNP/complementary 3′ and 5′ termini of vRNA (flu B virus)</td><td align="left" valign="top" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b28-viruses-01-00523">28</xref>,<xref ref-type="bibr" rid="b39-viruses-01-00523">39</xref>,<xref ref-type="bibr" rid="b55-viruses-01-00523">55</xref>]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">LaCrosse V. (-ssRNA, segm.)</td><td align="left" valign="top" rowspan="1" colspan="1">–</td><td align="left" valign="top" rowspan="1" colspan="1">panhandle structure of vRNA?</td><td align="left" valign="top" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b39-viruses-01-00523">39</xref>,<xref ref-type="bibr" rid="b76-viruses-01-00523">76</xref>]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SenV (-ssRNA, non-segm.)</td><td align="left" valign="top" rowspan="1" colspan="1">–</td><td align="left" valign="top" rowspan="1" colspan="1">?</td><td align="left" valign="top" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b91-viruses-01-00523">91</xref>]</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">SenV C protein mutant, NDV Ulster strain (-ssRNA, non-segm.)</td><td align="left" valign="top" rowspan="1" colspan="1">+</td><td align="left" valign="top" rowspan="1" colspan="1">replication intermediates</td><td align="left" valign="top" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b91-viruses-01-00523">91</xref>]</td></tr></tbody></table></table-wrap><table-wrap id="t2-viruses-01-00523" position="float"><label>Table 2.</label><caption><p>Discussed viral gene products that inhibit PKR activation.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="middle" rowspan="1" colspan="1"><bold>Viral product</bold></th><th align="left" valign="middle" rowspan="1" colspan="1"><bold>Virus</bold></th><th align="left" valign="middle" rowspan="1" colspan="1"><bold>Mode of inhibition</bold></th></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">NS1</td><td align="left" valign="top" rowspan="1" colspan="1">influenza A virus</td><td align="left" valign="top" rowspan="1" colspan="1">direct interaction with PKR</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">NS1</td><td align="left" valign="top" rowspan="1" colspan="1">influenza B virus</td><td align="left" valign="top" rowspan="1" colspan="1">dsRNA-mediated interaction with PKR</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">NSs</td><td align="left" valign="top" rowspan="1" colspan="1">Rift Valley Fever virus</td><td align="left" valign="top" rowspan="1" colspan="1">proteasome-mediated degradation of PKR</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">VP35</td><td align="left" valign="top" rowspan="1" colspan="1">Ebola Virus</td><td align="left" valign="top" rowspan="1" colspan="1">unknown</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">pTRS1/pIRS1</td><td align="left" valign="top" rowspan="1" colspan="1">human CMV</td><td align="left" valign="top" rowspan="1" colspan="1">relocalization of PKR, interaction with PKR</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">m142/m143</td><td align="left" valign="top" rowspan="1" colspan="1">murine CMV</td><td align="left" valign="top" rowspan="1" colspan="1">relocalization of PKR, direct interaction with PKR</td></tr></tbody></table></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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