Skip to main content
Log in

Is the optimal pH for membrane fusion in host cells by avian influenza viruses related to host range and pathogenicity?

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Influenza viruses isolated from wild ducks do not replicate in chickens. This fact is not explained solely by the receptor specificity of the hemagglutinin (HA) from such viruses for target host cells. To investigate this restriction in host range, the fusion activities of HA molecules from duck and chicken influenza viruses were examined. Influenza viruses A/duck/Mongolia/54/2001 (H5N2) (Dk/MNG) and A/chicken/Ibaraki/1/2005 (H5N2) (Ck/IBR), which replicate only in their primary hosts, were used. The optimal pH for membrane fusion of Ck/IBR was 5.9, higher than that of Dk/MNG at 4.9. To assess the relationship between the optimal pH for fusion and the host range of avian influenza viruses, the optimal pH for fusion of 55 influenza virus strains isolated from ducks and chickens was examined. No correlation was found between the host range and optimal pH for membrane fusion by the viruses, and this finding applied also to the H5N1 highly pathogenic avian influenza viruses. The optimal pH for membrane fusion for avian influenza viruses was shown to not necessarily be correlated with their host range or pathogenicity in ducks and chickens.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Costello DA, Whittaker GR, Daniel S (2015) Variations in pH sensitivity, acid stability, and fusogenicity of three influenza virus H3 subtypes. J Virol 89:350–360

    Article  PubMed  Google Scholar 

  2. Daniels PS, Jeffries S, Yates P, Schild GC, Rogers GN, Paulson JC, Wharton SA, Douglas AR, Skehel JJ, Wiley DC (1987) The receptor-binding and membrane-fusion properties of influenza virus variants selected using anti-haemagglutinin monoclonal antibodies. EMBO J 6:1459–1465

    CAS  PubMed  PubMed Central  Google Scholar 

  3. DuBois RM, Zaraket H, Reddivari M, Heath RJ, White SW, Russell CJ (2011) Acid stability of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity. PLoS Pathog 7:e1002398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Giannecchini S, Campitelli L, Calzoletti L, De Marco MA, Azzi A, Donatelli I (2006) Comparison of in vitro replication features of H7N3 influenza viruses from wild ducks and turkeys: potential implications for interspecies transmission. J Gen Virol 87:171–175

    Article  CAS  PubMed  Google Scholar 

  5. Helenius A (1992) Unpacking the incoming influenza virus. Cell 69:577–578

    Article  CAS  PubMed  Google Scholar 

  6. Hiono T, Okamatsu M, Nishihara S, Takase-Yoden S, Sakoda Y, Kida H (2014) A chicken influenza virus recognizes fucosylated alpha2,3 sialoglycan receptors on the epithelial cells lining upper respiratory tracts of chickens. Virology 456–457:131–138

    Article  PubMed  Google Scholar 

  7. Hiono T, Okamatsu M, Yamamoto N, Ogasawara K, Endo M, Kuribayashi S, Shichinohe S, Motohashi Y, Chu D, Suzuki M, Ichikawa T, Nishi T, Matsuno K, Tanaka K, Tanigawa T, Hiroshi K, Sakoda Y (2016) Experimental infection of highly and low pathogenic avian influenza viruses to chickens, ducks, tree sparrows, jungle crows, and black rats for the evaluation of their roles in virus transmission. Vet Microbiol 182:108–115

    Article  PubMed  Google Scholar 

  8. Ito T, Couceiro JN, Kelm S, Baum LG, Krauss S, Castrucci MR, Donatelli I, Kida H, Paulson JC, Webster RG, Kawaoka Y (1998) Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol 72:7367–7373

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Kida H, Yanagawa R (1979) Isolation and characterization of influenza a viruses from wild free-flying ducks in Hokkaido, Japan. Zentralbl Bakteriol Orig A 224:135–143

    Google Scholar 

  10. Kida H, Webster RG, Yanagawa R (1983) Inhibition of virus-induced hemolysis with monoclonal antibodies to different antigenic areas on the hemagglutinin molecule of A/seal/Massachusetts/1/80 (H7N7) influenza virus. Arch Virol 76:91–99

    Article  CAS  PubMed  Google Scholar 

  11. Lakadamyali M, Rust MJ, Zhuang X (2004) Endocytosis of influenza viruses. Microbes Infect 6:929–936

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lin YP, Wharton SA, Martin J, Skehel JJ, Wiley DC, Steinhauer DA (1997) Adaptation of egg-grown and transfectant influenza viruses for growth in mammalian cells: selection of hemagglutinin mutants with elevated pH of membrane fusion. Virology 233:402–410

    Article  CAS  PubMed  Google Scholar 

  13. Matrosovich MN, Gambaryan AS, Teneberg S, Piskarev VE, Yamnikova SS, Lvov DK, Robertson JS, Karlsson KA (1997) Avian influenza A viruses differ from human viruses by recognition of sialyloligosaccharides and gangliosides and by a higher conservation of the HA receptor-binding site. Virology 233:224–234

    Article  CAS  PubMed  Google Scholar 

  14. Murakami S, Horimoto T, Ito M, Takano R, Katsura H, Shimojima M, Kawaoka Y (2012) Enhanced growth of influenza vaccine seed viruses in vero cells mediated by broadening the optimal pH range for virus membrane fusion. J Virol 86:1405–1410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. O’Donnell CD, Vogel L, Matsuoka Y, Jin H, Subbarao K (2014) The matrix gene segment destabilizes the acid and thermal stability of the hemagglutinin of pandemic live attenuated influenza virus vaccines. J Virol 88:12374–12384

    Article  PubMed  PubMed Central  Google Scholar 

  16. Okada A, Miura T, Takeuchi H (2003) Zinc- and pH-dependent conformational transition in a putative interdomain linker region of the influenza virus matrix protein M1. Biochemistry 42:1978–1984

    Article  CAS  PubMed  Google Scholar 

  17. Portela A, Digard P (2002) The influenza virus nucleoprotein: a multifunctional RNA-binding protein pivotal to virus replication. J Gen Virol 83:723–734

    Article  CAS  PubMed  Google Scholar 

  18. Reed LJ, Muench H (1938) A simple method of estimating fifty percent endpoint. Am J Hyg 27:493–497

    Google Scholar 

  19. Reed ML, Bridges OA, Seiler P, Kim JK, Yen HL, Salomon R, Govorkova EA, Webster RG, Russell CJ (2010) The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus pathogenicity and transmissibility in ducks. J Virol 84:1527–1535

    Article  CAS  PubMed  Google Scholar 

  20. Rogers GN, Paulson JC (1983) Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin. Virology 127:361–373

    Article  CAS  PubMed  Google Scholar 

  21. Sakoda Y, Sugar S, Batchluun D, Erdene-Ochir TO, Okamatsu M, Isoda N, Soda K, Takakuwa H, Tsuda Y, Yamamoto N, Kishida N, Matsuno K, Nakayama E, Kajihara M, Yokoyama A, Takada A, Sodnomdarjaa R, Kida H (2010) Characterization of H5N1 highly pathogenic avian influenza virus strains isolated from migratory waterfowl in Mongolia on the way back from the southern Asia to their northern territory. Virology 406:88–94

    Article  CAS  PubMed  Google Scholar 

  22. Schnell JR, Chou JJ (2008) Structure and mechanism of the M2 proton channel of influenza A virus. Nature 451:591–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y (2006) Avian flu: influenza virus receptors in the human airway. Nature 440:435–436

    Article  CAS  PubMed  Google Scholar 

  24. Skehel JJ, Bayley PM, Brown EB, Martin SR, Waterfield MD, White JM, Wilson IA, Wiley DC (1982) Changes in the conformation of influenza virus hemagglutinin at the pH optimum of virus-mediated membrane fusion. Proc Natl Acad Sci USA 79:968–972

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Stouffer AL, Acharya R, Salom D, Levine AS, Di Costanzo L, Soto CS, Tereshko V, Nanda V, Stayrook S, DeGrado WF (2008) Structural basis for the function and inhibition of an influenza virus proton channel. Nature 451:596–599

    Article  CAS  PubMed  Google Scholar 

  26. Suzuki Y, Ito T, Suzuki T, Holland RE Jr, Chambers TM, Kiso M, Ishida H, Kawaoka Y (2000) Sialic acid species as a determinant of the host range of influenza A viruses. J Virol 74:11825–11831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tannock GA, Bryce DA, Paul JA (1985) Evaluation of chicken kidney and chicken embryo kidney cultures for the large-scale growth of attenuated influenza virus master strain A/Ann/Arbor/6/60-ca. Vaccine 3:333–339

    Article  CAS  PubMed  Google Scholar 

  28. Tsuda Y, Isoda N, Sakoda Y, Kida H (2009) Factors responsible for plaque formation of A/duck/Siberia/272/1998 (H13N6) influenza virus on MDCK cells. Virus Res 140:194–198

    Article  CAS  PubMed  Google Scholar 

  29. Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y (1992) Evolution and ecology of influenza A viruses. Microbiological Rev 56:152–179

    CAS  Google Scholar 

  30. Yang W, Qu S, Liu Q, Zheng C (2009) Avian influenza virus A/chicken/Hubei/489/2004 (H5N1) induces caspase-dependent apoptosis in a cell-specific manner. Mol Cell Biochem 332:233–241

    Article  CAS  PubMed  Google Scholar 

  31. Yoden S, Kida H, Kuwabara M, Yanagawa R, Webster RG (1986) Spin-labeling of influenza virus hemagglutinin permits analysis of the conformational change at low pH and its inhibition by antibody. Virus Res 4:251–261

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by a grant from the Global Centers of Excellence Program from Japan Society for the Promotion of Science. The present work was also supported in part by J-GRID; the Japan Initiative for Global Research Network on Infectious Diseases and Japan Science and Technology Agency Basic Research Programs, JSPS KAKENHI 26850178, and the Program for Leading Graduate Schools (F01) from the Japan Society for the Promotion of Science.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroshi Kida.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Okamatsu, M., Motohashi, Y., Hiono, T. et al. Is the optimal pH for membrane fusion in host cells by avian influenza viruses related to host range and pathogenicity?. Arch Virol 161, 2235–2242 (2016). https://doi.org/10.1007/s00705-016-2902-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-016-2902-z

Keywords

Navigation