nach oben

Erschienen in:

20.05.2019 | Original Article

PB2 and hemagglutinin mutations confer a virulent phenotype on an H1N2 avian influenza virus in mice

verfasst von: Zhijun Yu, Zhiguang Ren, Yongkun Zhao, Kaihui Cheng, Weiyang Sun, Xinghai Zhang, Jiaqiang Wu, Hongbin He, Xianzhu Xia, Yuwei Gao

Erschienen in: Archives of Virology | Ausgabe 8/2019

Einloggen, um Zugang zu erhalten

Abstract

We previously obtained mouse-adapted variants of H1N2 avian influenza virus that contained PB2-L134H, PB2-I647L, PB2-D701N, HA-G228S, and M1-D231N mutations. Here, we analyzed the effects of these mutations on viral pathogenicity in a mammalian model. By evaluating the virulence of mouse-adapted H1N2 variants at different generations, we found that the PB2-D701N and HA-G228S mutations both contribute to the virulence of this virus in mammals. Furthermore, we found that the PB2-D701N and HA-G228S mutations both enhance the ability of the virus to replicate in vivo and in vitro and that the PB2-D701N substitution results in an expansion of viral tissue tropism. These results suggest that the PB2-D701N mutation and the HA-G228S mutation are the major mammalian determinants of H1N2 virus. These results help us to understand more about the mechanisms by which influenza viruses adapt to mammals, and monitoring of these mutations can be used in continuous influenza surveillance to assess the pandemic potential of avian influenza virus variants.

Abdelwhab EM, Veits J, Ulrich R, Kasbohm E, Teifke JP, Mettenleiter TC (2016) Composition of the hemagglutinin polybasic proteolytic cleavage motif mediates variable virulence of H7N7 avian influenza viruses. Sci Rep 6:39505CrossRefPubMedPubMedCentral

Arzey GG, Kirkland PD, Arzey KE, Frost M, Maywood P, Conaty S, Hurt AC, Deng YM, Iannello P, Barr I, Dwyer DE, Ratnamohan M, McPhie K, Selleck P (2012) Influenza virus A (H10N7) in chickens and poultry abattoir workers, Australia. Emerg Infect Dis 18:814–816CrossRefPubMedPubMedCentral

Ayllon J, Hale BG, Garcia-Sastre A (2012) Strain-specific contribution of NS1-activated phosphoinositide 3-kinase signaling to influenza A virus replication and virulence. J Virol 86:5366–5370CrossRefPubMedPubMedCentral

Berhane Y, Embury-Hyatt C, Leith M, Kehler H, Suderman M, Pasick J (2014) Pre-exposing Canada Geese (Branta canadensis) to a low-pathogenic H1N1 avian influenza virus protects them against H5N1 HPAI virus challenge. J Wildl Dis 50:84–97CrossRefPubMed

Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF, Senne DA, Krauss S, Shortridge KF, Webster RG (1998) Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 351:472–477CrossRefPubMed

Czudai-Matwich V, Otte A, Matrosovich M, Gabriel G, Klenk HD (2014) PB2 mutations D701N and S714R promote adaptation of an influenza H5N1 virus to a mammalian host. J Virol 88:8735–8742CrossRefPubMedPubMedCentral

de Wit E, Kawaoka Y, de Jong MD, Fouchier RA (2008) Pathogenicity of highly pathogenic avian influenza virus in mammals. Vaccine 26(Suppl 4):D54–58CrossRefPubMedPubMedCentral

DeDiego ML, Nogales A, Lambert-Emo K, Martinez-Sobrido L, Topham DJ (2016) NS1 protein mutation I64T affects interferon responses and virulence of circulating H3N2 human influenza A viruses. J Virol 90:9693–9711CrossRefPubMedPubMedCentral

Fan S, Deng G, Song J, Tian G, Suo Y, Jiang Y, Guan Y, Bu Z, Kawaoka Y, Chen H (2009) Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice. Virology 384:28–32CrossRefPubMed

10.

Fan S, Macken CA, Li C, Ozawa M, Goto H, Iswahyudi NF, Nidom CA, Chen H, Neumann G, Kawaoka Y (2013) Synergistic effect of the PDZ and p85beta-binding domains of the NS1 protein on virulence of an avian H5N1 influenza A virus. J Virol 87:4861–4871CrossRefPubMedPubMedCentral

11.

Fan S, Hatta M, Kim JH, Halfmann P, Imai M, Macken CA, Le MQ, Nguyen T, Neumann G, Kawaoka Y (2014) Novel residues in avian influenza virus PB2 protein affect virulence in mammalian hosts. Nat Commun 5:5021CrossRefPubMedPubMedCentral

12.

Gabriel G, Fodor E (2014) Molecular determinants of pathogenicity in the polymerase complex. Curr Top Microbiol Immunol 385:35–60PubMed

13.

Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W, Chen J, Jie Z, Qiu H, Xu K, Xu X, Lu H, Zhu W, Gao Z, Xiang N, Shen Y, He Z, Gu Y, Zhang Z, Yang Y, Zhao X, Zhou L, Li X, Zou S, Zhang Y, Li X, Yang L, Guo J, Dong J, Li Q, Dong L, Zhu Y, Bai T, Wang S, Hao P, Yang W, Zhang Y, Han J, Yu H, Li D, Gao GF, Wu G, Wang Y, Yuan Z, Shu Y (2013) Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med 368:1888–1897CrossRefPubMed

14.

Gray GC, McCarthy T, Capuano AW, Setterquist SF, Alavanja MC, Lynch CF (2008) Evidence for avian influenza A infections among Iowa’s agricultural workers. Influenza Other Respir Viruses 2:61–69CrossRefPubMedPubMedCentral

15.

Hatta M, Gao P, Halfmann P, Kawaoka Y (2001) Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293:1840–1842CrossRefPubMed

16.

He CQ, Liu YX, Wang HM, Hou PL, He HB, Ding NZ (2016) New genetic mechanism, origin and population dynamic of bovine ephemeral fever virus. Vet Microbiol 182:50–56CrossRefPubMed

17.

Hoffmann E, Stech J, Leneva I, Krauss S, Scholtissek C, Chin PS, Peiris M, Shortridge KF, Webster RG (2000) Characterization of the influenza A virus gene pool in avian species in southern China: was H6N1 a derivative or a precursor of H5N1? J Virol 74:6309–6315CrossRefPubMedPubMedCentral

18.

Hou P, Wang H, Zhao G, He C, He H (2017) Rapid detection of infectious bovine Rhinotracheitis virus using recombinase polymerase amplification assays. BMC Vet Res 13:386CrossRefPubMedPubMedCentral

19.

Hou P, Zhao G, He C, Wang H, He H (2018) Biopanning of polypeptides binding to bovine ephemeral fever virus G1 protein from phage display peptide library. BMC Vet Res 14:3CrossRefPubMedPubMedCentral

20.

Hu J, Hu Z, Song Q, Gu M, Liu X, Wang X, Hu S, Chen C, Liu H, Liu W, Chen S, Peng D, Liu X (2013) The PA-gene-mediated lethal dissemination and excessive innate immune response contribute to the high virulence of H5N1 avian influenza virus in mice. J Virol 87:2660–2672CrossRefPubMedPubMedCentral

21.

Jiao P, Tian G, Li Y, Deng G, Jiang Y, Liu C, Liu W, Bu Z, Kawaoka Y, Chen H (2008) A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. J Virol 82:1146–1154CrossRefPubMed

22.

Jiao P, Wei L, Song Y, Cui J, Song H, Cao L, Yuan R, Luo K, Liao M (2014) D701N mutation in the PB2 protein contributes to the pathogenicity of H5N1 avian influenza viruses but not transmissibility in guinea pigs. Front Microbiol 5:642CrossRefPubMedPubMedCentral

23.

Ke C, Mok CKP, Zhu W, Zhou H, He J, Guan W, Wu J, Song W, Wang D, Liu J, Lin Q, Chu DKW, Yang L, Zhong N, Yang Z, Shu Y, Peiris JSM (2017) Human infection with highly pathogenic avian influenza A(H7N9) virus. China. Emerg Infect Dis 23:1332–1340CrossRefPubMed

24.

Kobasa D, Takada A, Shinya K, Hatta M, Halfmann P, Theriault S, Suzuki H, Nishimura H, Mitamura K, Sugaya N, Usui T, Murata T, Maeda Y, Watanabe S, Suresh M, Suzuki T, Suzuki Y, Feldmann H, Kawaoka Y (2004) Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. Nature 431:703–707CrossRefPubMed

25.

Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci MR, Donatelli I, Kawaoka Y (2000) Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol 74:8502–8512CrossRefPubMedPubMedCentral

26.

Pappas C, Aguilar PV, Basler CF, Solorzano A, Zeng H, Perrone LA, Palese P, Garcia-Sastre A, Katz JM, Tumpey TM (2008) Single gene reassortants identify a critical role for PB1, HA, and NA in the high virulence of the 1918 pandemic influenza virus. Proc Natl Acad Sci USA 105:3064–3069CrossRefPubMed

27.

Reed LJ, Muench H (1938) A simple method for estimating fifty percent endpoints. Am J Hyg (Lond) 27:493–497

28.

Saito T, Lim W, Suzuki T, Suzuki Y, Kida H, Nishimura SI, Tashiro M (2001) Characterization of a human H9N2 influenza virus isolated in Hong Kong. Vaccine 20:125–133CrossRefPubMed

29.

Shinya K, Hamm S, Hatta M, Ito H, Ito T, Kawaoka Y (2004) PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice. Virology 320:258–266CrossRefPubMed

30.

Shu Y (2013) Human infection with H7N9 virus. N Engl J Med 369:880CrossRefPubMed

31.

Su S, Bi Y, Wong G, Gray GC, Gao GF, Li S (2015) Epidemiology, evolution, and recent outbreaks of avian influenza virus in China. J Virol 89:8671–8676CrossRefPubMedPubMedCentral

32.

Sun H, Cui P, Song Y, Qi Y, Li X, Qi W, Xu C, Jiao P, Liao M (2015) PB2 segment promotes high-pathogenicity of H5N1 avian influenza viruses in mice. Front Microbiol 6:73PubMedPubMedCentral

33.

Uraki R, Kiso M, Shinya K, Goto H, Takano R, Iwatsuki-Horimoto K, Takahashi K, Daniels RS, Hungnes O, Watanabe T, Kawaoka Y (2013) Virulence determinants of pandemic A(H1N1)2009 influenza virus in a mouse model. J Virol 87:2226–2233CrossRefPubMedPubMedCentral

34.

Wang H, Hou P, Zhao G, Yu L, Gao YW, He H (2018) Development and evaluation of serotype-specific recombinase polymerase amplification combined with lateral flow dipstick assays for the diagnosis of foot-and-mouth disease virus serotype A, O and Asia1. BMC Vet Res 14:359CrossRefPubMedPubMedCentral

35.

Ward AC (1995) Specific changes in the M1 protein during adaptation of influenza virus to mouse. Adv Virol 140:383–389

36.

Watanabe T, Kiso M, Fukuyama S, Nakajima N, Imai M, Yamada S, Murakami S, Yamayoshi S, Iwatsuki-Horimoto K, Sakoda Y, Takashita E, McBride R, Noda T, Hatta M, Imai H, Zhao D, Kishida N, Shirakura M, de Vries RP, Shichinohe S, Okamatsu M, Tamura T, Tomita Y, Fujimoto N, Goto K, Katsura H, Kawakami E, Ishikawa I, Watanabe S, Ito M, Sakai-Tagawa Y, Sugita Y, Uraki R, Yamaji R, Eisfeld AJ, Zhong G, Fan S, Ping J, Maher EA, Hanson A, Uchida Y, Saito T, Ozawa M, Neumann G, Kida H, Odagiri T, Paulson JC, Hasegawa H, Tashiro M, Kawaoka Y (2013) Characterization of H7N9 influenza A viruses isolated from humans. Nature 501:551–555CrossRefPubMedPubMedCentral

37.

Wu H, Peng X, Peng X, Wu N (2016) Amino acid substitutions involved in the adaptation of a novel highly pathogenic H5N2 avian influenza virus in mice. Virol J 13:159CrossRefPubMedPubMedCentral

38.

Yu Q, Liu L, Pu J, Zhao J, Sun Y, Shen G, Wei H, Zhu J, Zheng R, Xiong D, Liu X, Liu J (2013) Risk perceptions for avian influenza virus infection among poultry workers, China. Emerg Infect Dis 19:313–316CrossRefPubMedPubMedCentral

39.

Yu Z, Sun W, Zhang X, Cheng K, Zhao C, Xia X, Gao Y (2017) Rapid acquisition adaptive amino acid substitutions involved in the virulence enhancement of an H1N2 avian influenza virus in mice. Vet Microbiol 207:97–102CrossRefPubMed

40.

Zhang H, de Vries RP, Tzarum N, Zhu X, Yu W, McBride R, Paulson JC, Wilson IA (2015) A human-infecting H10N8 influenza virus retains a strong preference for avian-type receptors. Cell Host Microbe 17:377–384CrossRefPubMedPubMedCentral

41.

Zhao G, Hou P, Huan Y, He C, Wang H, He H (2018) Development of a recombinase polymerase amplification combined with a lateral flow dipstick assay for rapid detection of the Mycoplasma bovis. BMC Vet Res 14:412CrossRefPubMedPubMedCentral

42.

Zhao G, Wang H, Hou P, He C, He H (2018) Rapid visual detection of Mycobacterium avium subsp. paratuberculosis by recombinase polymerase amplification combined with a lateral flow dipstick. J Vet Sci 19:242–250CrossRefPubMedPubMedCentral

Titel: PB2 and hemagglutinin mutations confer a virulent phenotype on an H1N2 avian influenza virus in mice
verfasst von: Zhijun Yu
Zhiguang Ren
Yongkun Zhao
Kaihui Cheng
Weiyang Sun
Xinghai Zhang
Jiaqiang Wu
Hongbin He
Xianzhu Xia
Yuwei Gao
Publikationsdatum: 20.05.2019
Verlag: Springer Vienna
Erschienen in: Archives of Virology / Ausgabe 8/2019
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-019-04283-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren.

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2019

An isolate of sweet potato chlorotic stunt virus from Brazil with a distinct genome organization

Complete genome characterization of three enterovirus C96 isolates in China

Isolation and complete genome sequence analysis of a novel ovine adenovirus type representing a possible new mastadenovirus species

A novel bat-associated circovirus identified in northern Hokkaido, Japan

Epidemiology of blood-borne viral infections in Afghanistan