The PB2 Polymerase Host Adaptation Substitutions Prime Avian Indonesia Sub Clade 2.1 H5N1 Viruses for Infecting Humans
Identifieur interne : 000041 ( Main/Exploration ); précédent : 000040; suivant : 000042The PB2 Polymerase Host Adaptation Substitutions Prime Avian Indonesia Sub Clade 2.1 H5N1 Viruses for Infecting Humans
Auteurs : Pui Wang ; Wenjun Song [République populaire de Chine] ; Bobo Wing-Yee Mok ; Min Zheng ; Siu-Ying Lau ; Siwen Liu ; Pin Chen ; Xiaofeng Huang ; Honglian Liu ; Conor J. Cremin ; Honglin ChenSource :
- Viruses [ 1999-4915 ] ; 2019.
Abstract
Significantly higher numbers of human infections with H5N1 virus have occurred in Indonesia and Egypt, compared with other affected areas, and it is speculated that there are specific viral factors for human infection with avian H5N1 viruses in these locations. We previously showed PB2-K526R is present in 80% of Indonesian H5N1 human isolates, which lack the more common PB2-E627K substitution. Testing the hypothesis that this mutation may prime avian H5N1 virus for human infection, we showed that: (1) K526R is rarely found in avian influenza viruses but was identified in H5N1 viruses 2–3 years after the virus emerged in Indonesia, coincident with the emergence of H5N1 human infections in Indonesia; (2) K526R is required for efficient replication of Indonesia H5N1 virus in mammalian cells in vitro and in vivo and reverse substitution to 526K in human isolates abolishes this ability; (3) Indonesian H5N1 virus, which contains K526R-PB2, is stable and does not further acquire E627K following replication in infected mice; and (4) virus containing K526R-PB2 shows no fitness deficit in avian species. These findings illustrate an important mechanism in which a host adaptive mutation that predisposes avian H5N1 virus towards infecting humans has arisen with the virus becoming prevalent in avian species prior to human infections occurring. A similar mechanism is observed in the Qinghai-lineage H5N1 viruses that have caused many human cases in Egypt; here, E627K predisposes towards human infections. Surveillance should focus on the detection of adaptation markers in avian strains that prime for human infection.
Url:
DOI: 10.3390/v11030292
PubMed: 30909490
PubMed Central: 6480796
Affiliations:
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(C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-viruses-11-00292">State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine, Guangzhou Medical University, Guangzhou 510180, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine, Guangzhou Medical University, Guangzhou 510180</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></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><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Zheng, Min" sort="Zheng, Min" uniqKey="Zheng M" first="Min" last="Zheng">Min Zheng</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></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><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Liu, Siwen" sort="Liu, Siwen" uniqKey="Liu S" first="Siwen" last="Liu">Siwen Liu</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Pin" sort="Chen, Pin" uniqKey="Chen P" first="Pin" last="Chen">Pin Chen</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Huang, Xiaofeng" sort="Huang, Xiaofeng" uniqKey="Huang X" first="Xiaofeng" last="Huang">Xiaofeng Huang</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Liu, Honglian" sort="Liu, Honglian" uniqKey="Liu H" first="Honglian" last="Liu">Honglian Liu</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Cremin, Conor J" sort="Cremin, Conor J" uniqKey="Cremin C" first="Conor J." last="Cremin">Conor J. Cremin</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30909490</idno><idno type="pmc">6480796</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480796</idno><idno type="RBID">PMC:6480796</idno><idno type="doi">10.3390/v11030292</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000C48</idno><idno type="wicri:explorRef" 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id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-viruses-11-00292">State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine, Guangzhou Medical University, Guangzhou 510180, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine, Guangzhou Medical University, Guangzhou 510180</wicri:regionArea><placeName><settlement type="city">Jiangmen</settlement><region type="province">Guangdong</region></placeName></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><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Zheng, Min" sort="Zheng, Min" uniqKey="Zheng M" first="Min" last="Zheng">Min Zheng</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></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><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Liu, Siwen" sort="Liu, Siwen" uniqKey="Liu S" first="Siwen" last="Liu">Siwen Liu</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Pin" sort="Chen, Pin" uniqKey="Chen P" first="Pin" last="Chen">Pin Chen</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Huang, Xiaofeng" sort="Huang, Xiaofeng" uniqKey="Huang X" first="Xiaofeng" last="Huang">Xiaofeng Huang</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Liu, Honglian" sort="Liu, Honglian" uniqKey="Liu H" first="Honglian" last="Liu">Honglian Liu</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Cremin, Conor J" sort="Cremin, Conor J" uniqKey="Cremin C" first="Conor J." last="Cremin">Conor J. Cremin</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><affiliation><nlm:aff id="af1-viruses-11-00292">State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology, and the Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China;<email>puiwang@hku.hk</email> (P.W.);<email>wjsong@hku.hk</email> (W.S.);<email>bobomok@hku.hk</email> (B.W.-Y.M.);<email>min.zheng@stjude.org</email> (M.Z.);<email>sylau926@hku.hk</email> (S.-Y.L.);<email>siwen531@CONNECT.HKU.HK</email> (S.L.);<email>u3508816@connect.hku.hk</email> (P.C.);<email>stevehxf@connect.hku.hk</email> (X.H.);<email>lhlotus@connect.hku.hk</email> (H.L.);<email>conor93@connect.hku.hk</email> (C.J.C.)</nlm:aff></affiliation></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Significantly higher numbers of human infections with H5N1 virus have occurred in Indonesia and Egypt, compared with other affected areas, and it is speculated that there are specific viral factors for human infection with avian H5N1 viruses in these locations. We previously showed PB2-K526R is present in 80% of Indonesian H5N1 human isolates, which lack the more common PB2-E627K substitution. Testing the hypothesis that this mutation may prime avian H5N1 virus for human infection, we showed that: (1) K526R is rarely found in avian influenza viruses but was identified in H5N1 viruses 2–3 years after the virus emerged in Indonesia, coincident with the emergence of H5N1 human infections in Indonesia; (2) K526R is required for efficient replication of Indonesia H5N1 virus in mammalian cells in vitro and in vivo and reverse substitution to 526K in human isolates abolishes this ability; (3) Indonesian H5N1 virus, which contains K526R-PB2, is stable and does not further acquire E627K following replication in infected mice; and (4) virus containing K526R-PB2 shows no fitness deficit in avian species. These findings illustrate an important mechanism in which a host adaptive mutation that predisposes avian H5N1 virus towards infecting humans has arisen with the virus becoming prevalent in avian species prior to human infections occurring. A similar mechanism is observed in the Qinghai-lineage H5N1 viruses that have caused many human cases in Egypt; here, E627K predisposes towards human infections. Surveillance should focus on the detection of adaptation markers in avian strains that prime for human infection.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.Y. Yuen</name></author><author><name sortKey="Chan, P K" uniqKey="Chan P">P.K. Chan</name></author><author><name sortKey="Peiris, M" uniqKey="Peiris M">M. Peiris</name></author><author><name sortKey="Tsang, D N" uniqKey="Tsang D">D.N. Tsang</name></author><author><name sortKey="Que, T L" uniqKey="Que T">T.L. 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Klenk</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country><region><li>Guangdong</li></region><settlement><li>Jiangmen</li></settlement></list><tree><noCountry><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name><name sortKey="Chen, Pin" sort="Chen, Pin" uniqKey="Chen P" first="Pin" last="Chen">Pin Chen</name><name sortKey="Cremin, Conor J" sort="Cremin, Conor J" uniqKey="Cremin C" first="Conor J." last="Cremin">Conor J. Cremin</name><name sortKey="Huang, Xiaofeng" sort="Huang, Xiaofeng" uniqKey="Huang X" first="Xiaofeng" last="Huang">Xiaofeng Huang</name><name sortKey="Lau, Siu Ying" sort="Lau, Siu Ying" uniqKey="Lau S" first="Siu-Ying" last="Lau">Siu-Ying Lau</name><name sortKey="Liu, Honglian" sort="Liu, Honglian" uniqKey="Liu H" first="Honglian" last="Liu">Honglian Liu</name><name sortKey="Liu, Siwen" sort="Liu, Siwen" uniqKey="Liu S" first="Siwen" last="Liu">Siwen Liu</name><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><name sortKey="Wang, Pui" sort="Wang, Pui" uniqKey="Wang P" first="Pui" last="Wang">Pui Wang</name><name sortKey="Zheng, Min" sort="Zheng, Min" uniqKey="Zheng M" first="Min" last="Zheng">Min Zheng</name></noCountry><country name="République populaire de Chine"><region name="Guangdong"><name sortKey="Song, Wenjun" sort="Song, Wenjun" uniqKey="Song W" first="Wenjun" last="Song">Wenjun Song</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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