Skip to main content
Log in

Effect of gene constellation and postreassortment amino acid change on the phenotypic features of H5 influenza virus reassortants

  • Published:
Archives of Virology Aims and scope Submit manuscript

Summary.

Reassortants between a low-pathogenic avian influenza virus strain A/Duck/Primorie/2621/2001 (H5N2) and a high-yield human influenza virus strain A/Puerto Rico/8/34 (H1N1) were generated, genotyped and analyzed with respect to their yield in embryonated chicken eggs, pathogenicity for mice, and immunogenicity. A reassortant having HA and NA genes from A/Duck/Primorie/2621/2001 virus and 6 genes from A/Puerto Rico/8/34 virus (6:2 reassortant) replicated efficiently in embryonated chicken eggs, the yields being intermediate between the yields of the avian parent virus and those of the A/Puerto Rico/8/34 parent strain. The reassortant having the HA gene from A/Duck/Primorie/2621/2001 virus and 7 genes from A/Puerto Rico/8/34 virus (7:1 reassortant) produced low yields. A variant of the 7:1 reassortant selected by serial passages in eggs had an amino acid substitution in the hemagglutinin (N244D, H3 numbering). The variant produced yields similar to those of the 6:2 reassortant. A 5:3 reassortant generated by a back-cross of the 6:2 reassortant with the avian parent and having PB1, HA and NA genes of A/Duck/Primorie/2621/2001 virus produced higher yields than the 7:1 or 6:2 reassortants, although still lower than the yields of A/Puerto Rico/8/34 virus. The 7:1, 6:2 and 5:3 reassortants were pathogenic for mice, with the level of virulence close to A/Puerto Rico/8/34 virus, in contrast to the extremely low pathogenicity of the A/Duck/Primorie/2621/2001 parent strain. Immunization of mice with an inactivated 6:2 H5N2 reassortant provided efficient immune protection against a reassortant virus containing the HA and NA genes of a recent H5N1 isolate. The results are discussed in connection with the problem of the improvement of vaccine strains against the threatening H5N1 pandemic.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • E Hoffmann AS Lipatov RJ Webby EA Govorkova RG Webster (2005) ArticleTitleRole of specific hemagglutinin amino acids in the immunogenicity and protection of H5N1 influenza virus vaccines Proc Natl Acad Sci USA 102 12915–12920 Occurrence Handle16118277 Occurrence Handle10.1073/pnas.0506416102 Occurrence Handle1:CAS:528:DC%2BD2MXhtVWktb%2FI

    Article  PubMed  CAS  Google Scholar 

  • NV Kaverin IA Rudneva YA Smirnov NN Finskaya (1988) ArticleTitleHuman-avian influenza virus reassortants: effect of reassortment pattern on multi-cycle reproduction in MDCK cells Arch Virol 103 117–126 Occurrence Handle3214268 Occurrence Handle10.1007/BF01319813 Occurrence Handle1:CAS:528:DyaL1MXhtlWqu7o%3D

    Article  PubMed  CAS  Google Scholar 

  • NV Kaverin AS Gambaryan NV Bovin IA Rudneva AA Shilov OM Khodova NL Varich BV Sinitsin NV Makarova EA Kropotkina (1998) ArticleTitlePostreassortment changes in influenza A virus hemagglutinin restoring HA-NA functional match Virology 244 315–321 Occurrence Handle9601502 Occurrence Handle10.1006/viro.1998.9119 Occurrence Handle1:CAS:528:DyaK1cXjtFahsL0%3D

    Article  PubMed  CAS  Google Scholar 

  • NV Kaverin MN Matrosovich AS Gambaryan IA Rudneva AA Shilov NL Varich NV Makarova EA Kropotkina BV Sinitsin (2000) ArticleTitleIntergenic HA-NA interactions in influenza A virus: postreassortment substitutions of charged amino acid in the hemagglutinin of different subtypes Virus Res 66 123–129 Occurrence Handle10725545 Occurrence Handle10.1016/S0168-1702(99)00131-8 Occurrence Handle1:CAS:528:DC%2BD3cXhvV2lsL8%3D

    Article  PubMed  CAS  Google Scholar 

  • ED Kilbourne (2004) ArticleTitleInfluenza pandemics: can we predict for the unpredictable? Viral Immunol 17 350–357 Occurrence Handle15357901 Occurrence Handle10.1089/vim.2004.17.350 Occurrence Handle1:CAS:528:DC%2BD2cXntlequ7w%3D

    Article  PubMed  CAS  Google Scholar 

  • CW Lee DA Senne DL Suarez (2004) ArticleTitleGeneration of reassortant influenza vaccines by reverse genetics that allows utilization of DIVA (differentiating infected from vaccinated animals strategy for the control of avian influenza Vaccine 22 3175–3181 Occurrence Handle15297071 Occurrence Handle10.1016/j.vaccine.2004.01.055 Occurrence Handle1:CAS:528:DC%2BD2cXmsVCqt7c%3D

    Article  PubMed  CAS  Google Scholar 

  • AS Lipatov EA Govorkova AJ Webby H Ozaki M Peiris Y Guan L Poon RG Webster (2004) ArticleTitleInfluenza: emergence and control J Virol 78 8951–8959 Occurrence Handle15308692 Occurrence Handle10.1128/JVI.78.17.8951-8959.2004 Occurrence Handle1:CAS:528:DC%2BD2cXntVKiur4%3D

    Article  PubMed  CAS  Google Scholar 

  • M Liu JM Wood T Ellis S Krauss P Seiler C Johnson E Hoffman J Humberd D Hulse Y Zhang RG Webster DR Perez (2003) ArticleTitlePreparation of a standardized, efficacious agricultural H5N3 vaccine by reverse genetics Virology 314 580–590 Occurrence Handle14554086 Occurrence Handle10.1016/S0042-6822(03)00458-6 Occurrence Handle1:CAS:528:DC%2BD3sXnvFSisbk%3D

    Article  PubMed  CAS  Google Scholar 

  • DK Lvov SS Yamnikova IT Fedyakina et al. (2004) ArticleTitleEcology and evolution of influenza viruses in Russia Probl Virol 49 IssueID#3 17–24 Occurrence Handle1:STN:280:DC%2BD2c3ovVKhtQ%3D%3D

    CAS  Google Scholar 

  • KG Nicholson AE Colegate A Podda I Stephenson J Wood E Ypma MC Zambon (2001) ArticleTitleSafety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomized trial of two potential vaccines against H5N1 influenza Lancet 357 1937–1943 Occurrence Handle11425416 Occurrence Handle10.1016/S0140-6736(00)05066-2 Occurrence Handle1:CAS:528:DC%2BD3MXks1OisLY%3D

    Article  PubMed  CAS  Google Scholar 

  • C Nicolson D Major JM Wood JS Robertson (2005) ArticleTitleGeneration of influenza vaccine viruses on Vero cells by reverse genetics: an H5N1 candidate vaccine strain produced under a quality system Vaccine 23 2943–2952 Occurrence Handle15780743 Occurrence Handle10.1016/j.vaccine.2004.08.054 Occurrence Handle1:CAS:528:DC%2BD2MXisVWktLo%3D

    Article  PubMed  CAS  Google Scholar 

  • LJ Reed H Muench (1938) ArticleTitleA simple method for estimating 50% endpoints Am J Hyg 27 493–497

    Google Scholar 

  • JL Schulman P Palese (1976) ArticleTitleSelection and identification of influenza virus recombinants of defined genetic composition J Virol 20 248–254 Occurrence Handle978791 Occurrence Handle1:CAS:528:DyaE28XlvV2ju7c%3D

    PubMed  CAS  Google Scholar 

  • K Subarrao H Chen D Swayne L Mingay E Fodor G Brownlee X Xu X Lu J Katz N Cox Y Matsuoka (2003) ArticleTitleEvaluation of a genetically modified reassortant H5N1 influenza virus vaccine candidate generated by plasmid-based reverse genetics Virology 305 192–200 Occurrence Handle10.1006/viro.2002.1742

    Article  Google Scholar 

  • A Takada N Kuboki K Okazaki A Ninomiya H Tanaka H Ozaki S Itamura H Nishimura M Enami M Tashiro KF Shortridge H Kida (1999) ArticleTitleAvirulent avian influenza virus as a vaccine strain against a potential human pandemic J Virol 73 8303–8307 Occurrence Handle10482580 Occurrence Handle1:CAS:528:DyaK1MXlvFyrtLw%3D

    PubMed  CAS  Google Scholar 

  • G Tian S Zhang Y Li Z Bu P Liu J Zhou C Li J Shi K Yu H Chen (2005) ArticleTitleProtective efficacy in chickens, geese and ducks of an H5N1-inactivated vaccine developed by reverse genetics Virology 341 153–162 Occurrence Handle16084554 Occurrence Handle10.1016/j.virol.2005.07.011 Occurrence Handle1:CAS:528:DC%2BD2MXhtVKjs73F

    Article  PubMed  CAS  Google Scholar 

  • RJ Webby DR Perez JS Coleman et al. (2004) ArticleTitleResponsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines Lancet 363 1099–1103 Occurrence Handle15064027 Occurrence Handle10.1016/S0140-6736(04)15892-3 Occurrence Handle1:STN:280:DC%2BD2c7ntFemtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • RG Webster WJ Bean OT Gorman TM Chambers Y Kawaoka (1992) ArticleTitleEvolution and ecology of influenza A viruses Microbiol Rev 56 152–179 Occurrence Handle1579108 Occurrence Handle1:STN:280:By2B2M3nvFM%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rudneva, I., Timofeeva, T., Shilov, A. et al. Effect of gene constellation and postreassortment amino acid change on the phenotypic features of H5 influenza virus reassortants. Arch Virol 152, 1139–1145 (2007). https://doi.org/10.1007/s00705-006-0931-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-006-0931-8

Keywords

Navigation