The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication
Identifieur interne : 000657 ( Main/Exploration ); précédent : 000656; suivant : 000658The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication
Auteurs : Wenjun Song [République populaire de Chine] ; Pui Wang [République populaire de Chine] ; Bobo Wing-Yee Mok [République populaire de Chine] ; Siu-Ying Lau [République populaire de Chine] ; Xiaofeng Huang [République populaire de Chine] ; Wai-Lan Wu [République populaire de Chine] ; Min Zheng [République populaire de Chine] ; Xi Wen [République populaire de Chine] ; Shigui Yang [République populaire de Chine] ; Yu Chen [République populaire de Chine] ; Lanjuan Li [République populaire de Chine] ; Kwok-Yung Yuen [République populaire de Chine] ; Honglin Chen [République populaire de Chine]Source :
- Nature Communications [ 2041-1723 ] ; 2014.
Abstract
Host-adaptive strategies, such as the E627K substitution in the PB2 protein, are critical for replication of avian influenza A viruses in mammalian hosts. Here we show that mutation PB2-K526R is present in some human H7N9 influenza isolates, in nearly 80% of H5N1 human isolates from Indonesia and, in conjunction with E627K, in almost all seasonal H3N2 viruses since 1970. Polymerase complexes containing PB2-526R derived from H7N9, H5N1 or H3N2 viruses exhibit increased polymerase activity. PB2-526R also enhances viral transcription and replication in cells. In comparison with viruses carrying 627K, H7N9 viruses carrying both 526R and 627K replicate more efficiently in mammalian (but not avian) cells and in mouse lung tissues, and cause greater body weight loss and mortality in infected mice. PB2-K526R interacts with nuclear export protein and our results suggest that it contributes to enhance replication for certain influenza virus subtypes, particularly in combination with 627K.
Url:
DOI: 10.1038/ncomms6509
PubMed: 25409547
PubMed Central: 4263149
Affiliations:
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replication</title><author><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Pui" sort="Wang, Pui" 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of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Shigui" sort="Yang, Shigui" uniqKey="Yang S" first="Shigui" last="Yang">Shigui Yang</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name 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for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25409547</idno><idno type="pmc">4263149</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263149</idno><idno type="RBID">PMC:4263149</idno><idno 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replication</title><author><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Pui" sort="Wang, Pui" uniqKey="Wang P" first="Pui" last="Wang">Pui Wang</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mok, Bobo Wing Yee" sort="Mok, Bobo Wing Yee" uniqKey="Mok B" first="Bobo Wing-Yee" last="Mok">Bobo Wing-Yee Mok</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lau, Siu Ying" sort="Lau, Siu Ying" uniqKey="Lau S" first="Siu-Ying" last="Lau">Siu-Ying Lau</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Huang, Xiaofeng" sort="Huang, Xiaofeng" uniqKey="Huang X" first="Xiaofeng" last="Huang">Xiaofeng Huang</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wu, Wai Lan" sort="Wu, Wai Lan" uniqKey="Wu W" first="Wai-Lan" last="Wu">Wai-Lan Wu</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zheng, Min" sort="Zheng, Min" uniqKey="Zheng M" first="Min" last="Zheng">Min Zheng</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wen, Xi" sort="Wen, Xi" uniqKey="Wen X" first="Xi" last="Wen">Xi Wen</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Shigui" sort="Yang, Shigui" uniqKey="Yang S" first="Shigui" last="Yang">Shigui Yang</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Yu" sort="Chen, Yu" uniqKey="Chen Y" first="Yu" last="Chen">Yu Chen</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Li, Lanjuan" sort="Li, Lanjuan" uniqKey="Li L" first="Lanjuan" last="Li">Lanjuan Li</name><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Research Center of Infection and Immunology, The University of Hong Kong</institution>, Hong Kong SAR,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University</institution>, Hangzhou 310003,<country>China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Host-adaptive strategies, such as the E627K substitution in the PB2 protein, are critical for replication of
avian influenza A viruses in mammalian hosts. Here we show that mutation
PB2-K526R is present in some
human H7N9 influenza isolates, in nearly 80% of H5N1 human isolates from Indonesia
and, in conjunction with E627K, in almost all seasonal H3N2 viruses since 1970.
Polymerase complexes containing PB2-526R derived from H7N9, H5N1 or H3N2 viruses exhibit increased
polymerase activity. PB2-526R also
enhances viral transcription and replication in cells. In comparison with viruses
carrying 627K, H7N9 viruses carrying both 526R and 627K replicate more efficiently
in mammalian (but not avian) cells and in mouse lung tissues, and cause greater body
weight loss and mortality in infected mice. PB2-K526R interacts with nuclear export protein and our results
suggest that it contributes to enhance replication for certain influenza virus
subtypes, particularly in combination with 627K.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Naffakh, N" uniqKey="Naffakh N">N. Naffakh</name></author><author><name sortKey="Tomoiu, A" uniqKey="Tomoiu A">A. Tomoiu</name></author><author><name sortKey="Rameix Welti, M X0a A" uniqKey="Rameix Welti M">M.
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