1887

Abstract

Influenza vaccine strains (IVSs) contain the haemagglutinin (HA) and neuraminidase (NA) genome segments of relevant circulating strains in the genetic background of influenza A/PR/8/1934 virus (PR8). Previous work has shown that the nature of the PB1 segment may be a limiting factor for the efficient production of IVSs. Here, we showed that the PB1 segment (PB1) from the 2009 pandemic influenza A virus (IAV) A/Giessen/06/2009 (Gi wt, H1N1pdm) may help to resolve (some of) these limitations. We produced a set of recombinant PR8-derived viruses that contained (i) the HA and NA segments from representative IAV strains (H3N2, H5N1, H7N9, H9N2); (ii) the PB1 segment from PR8 or Gi wt, respectively; and (iii) the remaining five genome segments from PR8. Viruses containing the PB1 segment, together with the heterologous HA/NA segments and five PR8 segments (5+2+1), replicated to higher titres compared with their 6+2 counterparts containing six PR8 segments and the equivalent heterologous HA/NA segments. Compared with PB1-containing IVSs, viruses with the PB1 segment replicated to higher or similar titres in both cell culture and embryonated eggs, most profoundly IVSs of the H5N1 and H7N9 subtype, which are known to grow poorly in these systems. IVSs containing either the PB1 or the cognate PB1 segment of the respective specific HA/NA donor strain showed enhanced or similar virus replication levels. This study suggests that substitution of PB1 with the PB1 segment may greatly improve the large-scale production of PR8-derived IVSs, especially of those known to replicate poorly .

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2016-03-01
2024-04-19
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References

  1. Abt M., de Jonge J., Laue M., Wolff T. 2011; Improvement of H5N1 influenza vaccine viruses: influence of internal gene segments of avian and human origin on production and hemagglutinin content. Vaccine 29:5153–5162 [View Article][PubMed]
    [Google Scholar]
  2. Arranz R., Coloma R., Chichón F. J., Conesa J. J., Carrascosa J. L., Valpuesta J. M., Ortín J., Martín-Benito J. 2012; The structure of native influenza virion ribonucleoproteins. Science 338:1634–1637 [View Article][PubMed]
    [Google Scholar]
  3. Binh N. T., Wakai C., Kawaguchi A., Nagata K. 2013; The N-terminal region of influenza virus polymerase PB1 adjacent to the PA binding site is involved in replication but not transcription of the viral genome. Front Microbiol 4:398 [View Article][PubMed]
    [Google Scholar]
  4. Chakrabarti A. K., Pasricha G. 2013; An insight into the PB1F2 protein and its multifunctional role in enhancing the pathogenicity of the influenza A viruses. Virology 440:97–104 [View Article][PubMed]
    [Google Scholar]
  5. Chen C. J., Chen G. W., Wang C. H., Huang C. H., Wang Y. C., Shih S. R. 2010; Differential localization and function of PB1-F2 derived from different strains of influenza A virus. J Virol 84:10051–10062 [View Article][PubMed]
    [Google Scholar]
  6. Cobbin J. C., Verity E. E., Gilbertson B. P., Rockman S. P., Brown L. E. 2013; The source of the PB1 gene in influenza vaccine reassortants selectively alters the hemagglutinin content of the resulting seed virus. J Virol 87:5577–5585 [View Article][PubMed]
    [Google Scholar]
  7. Compans R. W., Content J., Duesberg P. H. 1972; Structure of the ribonucleoprotein of influenza virus. J Virol 10:795–800[PubMed]
    [Google Scholar]
  8. Fodor E., Palese P., Brownlee G. G., García-Sastre A. 1998; Attenuation of influenza A virus mRNA levels by promoter mutations. J Virol 72:6283–6290[PubMed]
    [Google Scholar]
  9. Fulvini A. A., Ramanunninair M., Le J., Pokorny B. A., Arroyo J. M., Silverman J., Devis R., Bucher D. 2011; Gene constellation of influenza A virus reassortants with high growth phenotype prepared as seed candidates for vaccine production. PLoS One 6:e20823 [View Article][PubMed]
    [Google Scholar]
  10. Garten R. J., Davis C. T., Russell C. A., Shu B., Lindstrom S., Balish A., Sessions W. M., Xu X., Skepner E., other authors. 2009; Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 325:197–201 [View Article][PubMed]
    [Google Scholar]
  11. González S., Zürcher T., Ortín J. 1996; Identification of two separate domains in the influenza virus PB1 protein involved in the interaction with the PB2 and PA subunits: a model for the viral RNA polymerase structure. Nucleic Acids Res 24:4456–4463 [View Article][PubMed]
    [Google Scholar]
  12. Harvey R., Guilfoyle K. A., Roseby S., Robertson J. S., Engelhardt O. G. 2011; Improved antigen yield in pandemic H1N1(2009) candidate vaccine viruses with chimeric hemagglutinin molecules. J Virol 85:6086–6090 [View Article][PubMed]
    [Google Scholar]
  13. He X., Zhou J., Bartlam M., Zhang R., Ma J., Lou Z., Li X., Li J., Joachimiak A., other authors. 2008; Crystal structure of the polymerase PAC-PB1N complex from an avian influenza H5N1 virus. Nature 454:1123–1126 [View Article][PubMed]
    [Google Scholar]
  14. Hemerka J. N., Wang D., Weng Y., Lu W., Kaushik R. S., Jin J., Harmon A. F., Li F. 2009; Detection and characterization of influenza A virus PA-PB2 interaction through a bimolecular fluorescence complementation assay. J Virol 83:3944–3955 [View Article][PubMed]
    [Google Scholar]
  15. Hess R. D., Weber F., Watson K., Schmitt S. 2012; Regulatory, biosafety and safety challenges for novel cells as substrates for human vaccines. Vaccine 30:2715–2727 [View Article][PubMed]
    [Google Scholar]
  16. Hoffmann E., Neumann G., Kawaoka Y., Hobom G., Webster R. G. 2000; A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci U S A 97:6108–6113 [View Article][PubMed]
    [Google Scholar]
  17. Hoffmann E., Stech J., Guan Y., Webster R. G., Perez D. R. 2001; Universal primer set for the full-length amplification of all influenza A viruses. Arch Virol 146:2275–2289 [View Article][PubMed]
    [Google Scholar]
  18. Hoffmann E., Krauss S., Perez D., Webby R., Webster R. G. 2002; Eight-plasmid system for rapid generation of influenza virus vaccines. Vaccine 20:3165–3170 [View Article][PubMed]
    [Google Scholar]
  19. Hu W., Zhang H., Han Q., Li L., Chen Y., Xia N., Chen Z., Shu Y., Xu K., Sun B. 2015; A Vero-cell-adapted vaccine donor strain of influenza A virus generated by serial passages. Vaccine 33:374–381 [View Article][PubMed]
    [Google Scholar]
  20. Huang D., Peng W. J., Ye Q., Liu X. P., Zhao L., Fan L., Xia-Hou K., Jia H. J., Luo J., other authors. 2015; Serum-free suspension culture of MDCK cells for production of influenza H1N1 vaccines. PLoS One 10:e0141686 [View Article][PubMed]
    [Google Scholar]
  21. Jing X., Soto J., Gao Y., Phy K., Ye Z. 2013; Assessment of viral replication in eggs and HA protein yield of pre-pandemic H5N1 candidate vaccine viruses. Vaccine 31:4091–4097 [View Article][PubMed]
    [Google Scholar]
  22. Kawaoka Y., Krauss S., Webster R. G. 1989; Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol 63:4603–4608[PubMed]
    [Google Scholar]
  23. Le J., Orff E. J., Fulvini A. A., Huang L., Onodera S., Pokorny B. A., Malewicz A., Primakov P., Bucher D. J. 2015; Development of high yield reassortants for influenza type B viruses and analysis of their gene compositions. Vaccine 33:879–884 [View Article][PubMed]
    [Google Scholar]
  24. Mostafa A., Kanrai P., Ziebuhr J., Pleschka S. 2013; Improved dual promotor-driven reverse genetics system for influenza viruses. J Virol Methods 193:603–610 [View Article][PubMed]
    [Google Scholar]
  25. Mostafa A., Kanrai P., Petersen H., Ibrahim S., Rautenschlein S., Pleschka S. 2015; Efficient generation of recombinant influenza A viruses employing a new approach to overcome the genetic instability of HA segments. PLoS One 10:e0116917 [View Article][PubMed]
    [Google Scholar]
  26. Moulès V., Terrier O., Yver M., Riteau B., Moriscot C., Ferraris O., Julien T., Giudice E., Rolland J. P., other authors. 2011; Importance of viral genomic composition in modulating glycoprotein content on the surface of influenza virus particles. Virology 414:51–62 [View Article][PubMed]
    [Google Scholar]
  27. Naruse T., Fukuda T., Tanabe T., Ichikawa M., Oda Y., Tochihara S., Kimachi K., Kino Y., Ueda K. 2015; A clinical phase I study of an EB66 cell-derived H5N1 pandemic vaccine adjuvanted with AS03. Vaccine 33:6078–6084 [View Article][PubMed]
    [Google Scholar]
  28. Neumann G., Noda T., Kawaoka Y. 2009; Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 459:931–939 [View Article][PubMed]
    [Google Scholar]
  29. Ngai K. L., Chan M. C., Chan P. K. 2013; Replication and transcription activities of ribonucleoprotein complexes reconstituted from avian H5N1, H1N1pdm09 and H3N2 influenza A viruses. PLoS One 8:e65038 [View Article][PubMed]
    [Google Scholar]
  30. Obayashi E., Yoshida H., Kawai F., Shibayama N., Kawaguchi A., Nagata K., Tame J. R. H., Park S. Y. 2008; The structural basis for an essential subunit interaction in influenza virus RNA polymerase. Nature 454:1127–1131 [View Article][PubMed]
    [Google Scholar]
  31. Ozaki H., Govorkova E. A., Li C., Xiong X., Webster R. G., Webby R. J. 2004; Generation of high-yielding influenza A viruses in African green monkey kidney (Vero) cells by reverse genetics. J Virol 78:1851–1857 [View Article][PubMed]
    [Google Scholar]
  32. Peng J., Yang H., Jiang H., Lin Y. X., Lu C. D., Xu Y. W., Zeng J. 2014; The origin of novel avian influenza A (H7N9) and mutation dynamics for its human-to-human transmissible capacity. PLoS One 9:e93094 [View Article][PubMed]
    [Google Scholar]
  33. Plant E. P., Liu T. M., Xie H., Ye Z. 2012; Mutations to A/Puerto Rico/8/34 PB1 gene improves seasonal reassortant influenza A virus growth kinetics. Vaccine 31:207–212 [View Article][PubMed]
    [Google Scholar]
  34. Ramanunninair M., Le J., Onodera S., Fulvini A. A., Pokorny B. A., Silverman J., Devis R., Arroyo J. M., He Y.other authors 2013; Molecular signature of high yield (growth) influenza a virus reassortants prepared as candidate vaccine seeds. PLoS One 8:e65955 [View Article][PubMed]
    [Google Scholar]
  35. Ritchey M. B., Palese P., Kilbourne E. D. 1976; RNAs of influenza A, B, and C viruses. J Virol 18:738–744[PubMed]
    [Google Scholar]
  36. Schickli J. H., Flandorfer A., Nakaya T., Martinez-Sobrido L., García-Sastre A., Palese P. 2001; Plasmid-only rescue of influenza A virus vaccine candidates. Philos Trans R Soc Lond B Biol Sci 356:1965–1973 [View Article][PubMed]
    [Google Scholar]
  37. Shaw M. L., Palese P. 2013 Orthomyxoviridae Philadelphia: Lippincott Williams & Wilkins;
    [Google Scholar]
  38. Smith G. J., Bahl J., Vijaykrishna D., Zhang J., Poon L. L., Chen H., Webster R. G., Peiris J. S., Guan Y. 2009; Dating the emergence of pandemic influenza viruses. Proc Natl Acad Sci U S A 106:11709–11712 [View Article][PubMed]
    [Google Scholar]
  39. Subbarao K., Chen H., Swayne D., Mingay L., Fodor E., Brownlee G., Xu X., Lu X., Katz J., other authors. 2003; Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics. Virology 305:192–200 [View Article][PubMed]
    [Google Scholar]
  40. Sugiyama K., Obayashi E., Kawaguchi A., Suzuki Y., Tame J. R. H., Nagata K., Park S. Y. 2009; Structural insight into the essential PB1-PB2 subunit contact of the influenza virus RNA polymerase. EMBO J 28:1803–1811 [View Article][PubMed]
    [Google Scholar]
  41. Tong S., Li Y., Rivailler P., Conrardy C., Castillo D. A., Chen L. M., Recuenco S., Ellison J. A., Davis C. T., other authors. 2012; A distinct lineage of influenza A virus from bats. Proc Natl Acad Sci U S A 109:4269–4274 [View Article][PubMed]
    [Google Scholar]
  42. Tong S., Zhu X., Li Y., Shi M., Zhang J., Bourgeois M., Yang H., Chen X., Recuenco S., other authors. 2013; New world bats harbor diverse influenza A viruses. PLoS Pathog 9:e1003657 [View Article][PubMed]
    [Google Scholar]
  43. Ulmanen I., Broni B. A., Krug R. M. 1981; Role of two of the influenza virus core P proteins in recognizing cap 1 structures (m7GpppNm) on RNAs and in initiating viral RNA transcription. Proc Natl Acad Sci U S A 78:7355–7359 [View Article][PubMed]
    [Google Scholar]
  44. Wang Z., Robb N. C., Lenz E., Wolff T., Fodor E., Pleschka S. 2010; NS reassortment of an H7-type highly pathogenic avian influenza virus affects its propagation by altering the regulation of viral RNA production and antiviral host response. J Virol 84:11323–11335 [View Article][PubMed]
    [Google Scholar]
  45. Wanitchang A., Kramyu J., Jongkaewwattana A. 2010; Enhancement of reverse genetics-derived swine-origin H1N1 influenza virus seed vaccine growth by inclusion of indigenous polymerase PB1 protein. Virus Res 147:145–148 [View Article][PubMed]
    [Google Scholar]
  46. Wendel I., Rubbenstroth D., Doedt J., Kochs G., Wilhelm J., Staeheli P., Klenk H. D., Matrosovich M. 2015; The avian-origin PB1 gene segment facilitated replication and transmissibility of the H3N2/1968 pandemic influenza virus. J Virol 89:4170–4179 [View Article][PubMed]
    [Google Scholar]
  47. WHO 2009; Global surveillance during an influenza pandemic. Available at: http://www.who.int/csr/resources/publications/swineflu/surveillance/en/ (accessed 1 August 2014)
  48. Wille M., Tolf C., Avril A., Latorre-Margalef N., Wallerström S., Olsen B., Waldenström J. 2013; Frequency and patterns of reassortment in natural influenza A virus infection in a reservoir host. Virology 443:150–160 [View Article][PubMed]
    [Google Scholar]
  49. Yoon S. W., Webby R. J., Webster R. G. 2014; Evolution and ecology of influenza A viruses. Curr Top Microbiol Immunol 385:359–375[PubMed]
    [Google Scholar]
  50. Zhao X., Sun Y., Pu J., Fan L., Shi W., Hu Y., Yang J., Xu Q., Wang J., other authors. 2011; Characterization of an artificial swine-origin influenza virus with the same gene combination as H1N1/2009 virus: a genesis clue of pandemic strain. PLoS One 6:e22091 [View Article][PubMed]
    [Google Scholar]
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