PA-X: a key regulator of influenza A virus pathogenicity and host immune responses
Identifieur interne : 000235 ( Pmc/Curation ); précédent : 000234; suivant : 000236PA-X: a key regulator of influenza A virus pathogenicity and host immune responses
Auteurs : Jiao Hu [République populaire de Chine] ; Chunxi Ma [République populaire de Chine] ; Xiufan Liu [République populaire de Chine]Source :
- Medical Microbiology and Immunology [ 0300-8584 ] ; 2018.
Abstract
PA-X, a fusion protein belonging to influenza A viruses (IAVs), integrating the N-terminal 191 amino acids of PA gene and the ribosomal frame-shifting product that lengthens out to 41 or 61 amino acids. Since its discovery in 2012, multiple functions have been attributed to this small protein, including a process, where wide-spread protein synthesis in infected host cells is shut down (called host shutoff), and viral replication, polymerase activity, viral-induced cell apoptosis, PA nuclear localization, and virulence are modulated. However, many of its proposed functions may be specific to strain, subtype, host, or cell line. In this review, we start by describing the well-defined global host-shutoff ability of PA-X and the potential mechanisms underlying it. We move on to the role played by PA-X in modulating innate and acquired immune responses in the host. We then systematically discuss the role played by PA-X in modulating the virulence of influenza viruses of different subtypes and host origins, and finish with a general overview of the research advances made in identifying the host cell partners that interact with PA-X. To uncover possible clues about the differential effects of PA-X in modulating viral virulence, we focus on systemically evaluating polymorphisms in PA-X from various viral subtypes and hosts, including avian and human H5N1, H5N6, H9N2, and H7N9 viruses. Finally, we conclude with a proposition regarding the possible future research directions for this important protein.
Url:
DOI: 10.1007/s00430-018-0548-z
PubMed: 29974232
PubMed Central: 7086933
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<front><div type="abstract" xml:lang="en"><p id="Par1">PA-X, a fusion protein belonging to influenza A viruses (IAVs), integrating the N-terminal 191 amino acids of PA gene and the ribosomal frame-shifting product that lengthens out to 41 or 61 amino acids. Since its discovery in 2012, multiple functions have been attributed to this small protein, including a process, where wide-spread protein synthesis in infected host cells is shut down (called host shutoff), and viral replication, polymerase activity, viral-induced cell apoptosis, PA nuclear localization, and virulence are modulated. However, many of its proposed functions may be specific to strain, subtype, host, or cell line. In this review, we start by describing the well-defined global host-shutoff ability of PA-X and the potential mechanisms underlying it. We move on to the role played by PA-X in modulating innate and acquired immune responses in the host. We then systematically discuss the role played by PA-X in modulating the virulence of influenza viruses of different subtypes and host origins, and finish with a general overview of the research advances made in identifying the host cell partners that interact with PA-X. To uncover possible clues about the differential effects of PA-X in modulating viral virulence, we focus on systemically evaluating polymorphisms in PA-X from various viral subtypes and hosts, including avian and human H5N1, H5N6, H9N2, and H7N9 viruses. Finally, we conclude with a proposition regarding the possible future research directions for this important protein.</p>
</div>
</front>
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<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Med Microbiol Immunol</journal-id>
<journal-id journal-id-type="iso-abbrev">Med. Microbiol. Immunol</journal-id>
<journal-title-group><journal-title>Medical Microbiology and Immunology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0300-8584</issn>
<issn pub-type="epub">1432-1831</issn>
<publisher><publisher-name>Springer Berlin Heidelberg</publisher-name>
<publisher-loc>Berlin/Heidelberg</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">29974232</article-id>
<article-id pub-id-type="pmc">7086933</article-id>
<article-id pub-id-type="publisher-id">548</article-id>
<article-id pub-id-type="doi">10.1007/s00430-018-0548-z</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>PA-X: a key regulator of influenza A virus pathogenicity and host immune responses</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Hu</surname>
<given-names>Jiao</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ma</surname>
<given-names>Chunxi</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Liu</surname>
<given-names>Xiufan</given-names>
</name>
<address><phone>+86 514 87991416</phone>
<email>xfliu@yzu.edu.cn</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<aff id="Aff1"><label>1</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.268415.c</institution-id>
<institution>Animal Infectious Disease Laboratory, School of Veterinary Medicine,</institution>
<institution>Yangzhou University,</institution>
</institution-wrap>
48 East Wenhui Road, Yangzhou, 225009 Jiangsu Province China</aff>
<aff id="Aff2"><label>2</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.268415.c</institution-id>
<institution>Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis,</institution>
<institution>Yangzhou University,</institution>
</institution-wrap>
Yangzhou, Jiangsu China</aff>
<aff id="Aff3"><label>3</label>
<institution-wrap><institution-id institution-id-type="GRID">grid.268415.c</institution-id>
<institution>Key Laboratory of Prevention and Control of Biological Hazard Factors (Animal Origin) for Agri-food Safety and Quality, Ministry of Agriculture of China (26116120),</institution>
<institution>Yangzhou University,</institution>
</institution-wrap>
Yangzhou, China</aff>
</contrib-group>
<pub-date pub-type="epub"><day>4</day>
<month>7</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="ppub"><year>2018</year>
</pub-date>
<volume>207</volume>
<issue>5</issue>
<fpage>255</fpage>
<lpage>269</lpage>
<history><date date-type="received"><day>22</day>
<month>5</month>
<year>2018</year>
</date>
<date date-type="accepted"><day>28</day>
<month>6</month>
<year>2018</year>
</date>
</history>
<permissions><copyright-statement>© Springer-Verlag GmbH Germany, part of Springer Nature 2018</copyright-statement>
<license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p>
</license>
</permissions>
<abstract id="Abs1"><p id="Par1">PA-X, a fusion protein belonging to influenza A viruses (IAVs), integrating the N-terminal 191 amino acids of PA gene and the ribosomal frame-shifting product that lengthens out to 41 or 61 amino acids. Since its discovery in 2012, multiple functions have been attributed to this small protein, including a process, where wide-spread protein synthesis in infected host cells is shut down (called host shutoff), and viral replication, polymerase activity, viral-induced cell apoptosis, PA nuclear localization, and virulence are modulated. However, many of its proposed functions may be specific to strain, subtype, host, or cell line. In this review, we start by describing the well-defined global host-shutoff ability of PA-X and the potential mechanisms underlying it. We move on to the role played by PA-X in modulating innate and acquired immune responses in the host. We then systematically discuss the role played by PA-X in modulating the virulence of influenza viruses of different subtypes and host origins, and finish with a general overview of the research advances made in identifying the host cell partners that interact with PA-X. To uncover possible clues about the differential effects of PA-X in modulating viral virulence, we focus on systemically evaluating polymorphisms in PA-X from various viral subtypes and hosts, including avian and human H5N1, H5N6, H9N2, and H7N9 viruses. Finally, we conclude with a proposition regarding the possible future research directions for this important protein.</p>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd>Influenza virus</kwd>
<kwd>PA-X</kwd>
<kwd>Host shutoff</kwd>
<kwd>Immunomodulatory proteins</kwd>
<kwd>Pathogenesis</kwd>
<kwd>Virus–host interaction</kwd>
</kwd-group>
<funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100001809</institution-id>
<institution>National Natural Science Foundation of China</institution>
</institution-wrap>
</funding-source>
<award-id>31502076</award-id>
<principal-award-recipient><name><surname>Hu</surname>
<given-names>Jiao</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<funding-group><award-group><funding-source><institution>Jiangsu Provincial Natural Science Foundation of China</institution>
</funding-source>
<award-id>BK20150444</award-id>
<principal-award-recipient><name><surname>Hu</surname>
<given-names>Jiao</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<funding-group><award-group><funding-source><institution>National Key Research and Development Project of China</institution>
</funding-source>
<award-id>2016YFD0500202-1</award-id>
<principal-award-recipient><name><surname>Liu</surname>
<given-names>Xiufan</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100009997</institution-id>
<institution>Earmarked Fund for Modern Agro-industry Technology Research System</institution>
</institution-wrap>
</funding-source>
<award-id>nycytx-41-G07</award-id>
<principal-award-recipient><name><surname>Liu</surname>
<given-names>Xiufan</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<funding-group><award-group><funding-source><institution>Special Financial Grant from the China Postdoctoral Science Foundation</institution>
</funding-source>
<award-id>2016T90515</award-id>
<principal-award-recipient><name><surname>Liu</surname>
<given-names>Xiufan</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© Springer-Verlag GmbH Germany, part of Springer Nature 2018</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>
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