Skip to main content
Log in

Changes in the morphology of influenza particles induced at low pH

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

Summary

At low pH influenza virus causes membrane fusion. This phenomenon is thought to reflect a part of the infection mechanism of the virus. To obtain more information on the effect of low pH on the virus, the change in morphology of influenza virus particles was studied by electron microscopy. Further, the degradation of haemagglutinin (HA) after trypsin digestion as a function of pH was studied by gel electrophoresis. The results showed that a threshold value existed below which both a change in morphology and an increase in trypsin sensitivity were observed. This threshold pH was found to be strain specific. A number of strains showed a heterogeneity in the particle population with respect to the threshold pH. The various subpopulations appeared to differ genetically. Virus particles with uncleaved precursor HA, HAo, were not effected by the low pH treatment.

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.

Similar content being viewed by others

References

  1. Aymard-Henry, M., Coleman, M. T., Dowdle, W. R., Laver, W. G., Schild, G. C., Webster, R. G.: Influenza virus neuraminidase and neuraminidase-inhibition test procedures. Bull. Wld. Hlth. Org.49, 199–202 (1973).

    Google Scholar 

  2. Bancroft, J. B., Hills, G. J., Markham, R.: A study of the self-assembly process in a small spherical virus. Formation of organized structures from protein subunitsin vitro. Virology31, 354–379 (1967).

    Google Scholar 

  3. Bukrinskaya, A. G., Vorkunova, N. K., Kornilayeva, G. V., Narmanbetova, R. A., Vorkunova, G. K.: Influenza virus uncoating in infected cells and effect of rimantidine. J. gen. Virol.60, 49–59 (1982).

    Google Scholar 

  4. Daniels, R. A., Douglas, A. R., Skehel, J. J., Wiley, D. C.: Analysis of the antigenicity of influenza virus haemagglutinin at the pH optimum of virus mediated membrane fusion. J. gen. Virol.64, 1657–1662 (1983).

    Google Scholar 

  5. De Jong, J. C., de Ronde-Verloop, F. M., Veenendaal-van Herk, T. M.: Variability of influenza virus in respect to antigenic reactivity. Abstracts Regular Meeting European Association against Virus Disease, Munich, 1979.

  6. Draper, R. K., Simon, M. I.: The entry of diphteria toxin into the mammalian cell cytoplasm: evidence for lysosomal involvement. J. Cell Biol.87, 849–854 (1980).

    Google Scholar 

  7. Gething, M. J., White, J. M., Waterfield, M.: Purification of the fusion protein of sendai virus: Analysis of the NH2-terminal sequence generated during precursor activation. Proc. Natl. Acad. Sci. U.S.A.75, 2737–2740 (1978).

    Google Scholar 

  8. Gething, M. J., Bye, J., Skehel, J., Waterfield, M.: Cloning and DNA sequence of double stranded copies of haemagglutinin genes from H2 and H3 strains elucidates antigenic shift and drift in influenza virus. Nature287, 301–306 (1980).

    Google Scholar 

  9. Helenius, A., Kartenbeck, J., Simons, K., Fries, E.: On the entry of semliki forest virus into BHK-21 cells. J. Cell Biol.84, 404–420 (1980).

    Google Scholar 

  10. Helenius, A., Marsh, M., White, J.: Inhibition of semliki forest virus penetration by lysomotropic weak bases. J. gen. Virol.58, 47–61 (1982).

    Google Scholar 

  11. Hiti, A. L., Davies, A. R., Nayak, D. P.: Complete sequence analysis shows that the haemagglutinin of the H0 and H2 subtypes of human influenza virus are closely related. Virology111, 113–124 (1981).

    Google Scholar 

  12. Hosaka, Y., Seriburi, O., Moran, M. G., Yasuda, Y., Fukai, K., Nerome, K.: Haemolysis and fusion by influenza viruses with heat inactivated neuraminidase activity. Biken J.25, 51–62 (1982).

    Google Scholar 

  13. Huang, R. T., Rott, R., Klenk, H.-D.: Influenza virus causes haemolysis and fusion of cells. Virology110, 243–247 (1981).

    Google Scholar 

  14. Incardona, N. L., McKee, S., Flanagan, J. B.: Noncovalent interactions in viruses. Characterization of their role in the pH and thermally induced changes in bromegrass mosaic virus. Virology53, 204–214 (1973).

    Google Scholar 

  15. Jacrot, B.: Studies on the assembly of a spherical plant virus. II. The mechanism of protein aggregation and virus swelling. J. Mol. Biol.95, 433–446 (1975).

    Google Scholar 

  16. Klenk, H.-D., Rott, R., Ohrlich, M., Blodorn, J.: Activation of influenza A viruses by trypsin treatment. Virology68, 426–439 (1975).

    Google Scholar 

  17. Krystal, M., Elliot, R. M., Benz, E. W., Jr., Young, J. F., Palese, P.: Evolution of influenza A and B viruses: Conservation of structural features in the haemagglutinin genes. Proc. Natl. Acad. Sci. U.S.A.79, 4800–4804 (1982).

    Google Scholar 

  18. Krystal, M., Young, J. F., Palese, P., Wilson, I. A., Skehel, J. J., Wiley, D. C.: Sequential mutations in hemagglutinins of influenza B virus isolates: Definition of antigenic domains. Proc. Natl. Acad. Sci. U.S.A.80, 4527–4531 (1983).

    Google Scholar 

  19. Lazarowitz, S. G., Choppin, P. W.: Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide. Virology68, 440–454 (1975).

    Google Scholar 

  20. Lenard, J., Bailey, C. A., Miller, D. K.: pH dependence of influenza A virus-induced hemolysis is determined by the haemagglutinin gene. J. gen. Virol.62, 353–355 (1982).

    Google Scholar 

  21. Maeda, T., Ohnishi, S.-I.: Activation of influenza virus by acidic media causes hemolysis and fusion of erythrocytes. FEBS Lett.122, 283–287 (1980).

    Google Scholar 

  22. Maeda, T., Kawasaki, K., Ohnishi, S.-I.: Interaction of influenza virus hemagglutinin with target membrane lipids is a key step in virus induced hemolysis and fusion at pH 5.2. Proc. Natl. Acad. Sci. U.S.A.78, 4133–4137 (1981).

    Google Scholar 

  23. Matlin, K. S., Reggio, H., Helenius, A., Simons, K.: Infection entry pathway of influenza virus in a canine kidney cell line. J. Cell Biol.91, 601–603 (1981).

    Google Scholar 

  24. Min Jou, W., Verhoeyen, M., Devos, R., Samon, E., Fang, R., Huylebroek, D., Fiers, W.: Complete structure of the hemagglutinin gene from the human influenza A/Victoria/3/75 (H3N2) strain as determined from cloned DNA. Cell19, 683–696 (1980).

    Google Scholar 

  25. Pfeiffer, P., Durham, A. C. H.: The cation binding associated with structural transitions in bromegrass mosaic virus. Virology81, 419–432 (1977).

    Google Scholar 

  26. Porter, A. G., Barber, C., Carey, N. H., Hallewell, R. A., Threlfall, G., Emtage, J. S.: Complete nucleotide sequence of an influenza virus haemagglutinin gene from cloned DNA. Nature282, 471–477 (1979).

    Google Scholar 

  27. Sato, S. B., Kawasaki, K., Ohnishi, S.-I.: Hemolytic activity of influenza virus hemagglutinin glycoproteins activated in mildly acidic environments. Proc. Natl. Acad. Sci. U.S.A.80, 3153–3157 (1983).

    Google Scholar 

  28. Schild, G. C., Oxford, J. S., de Jong, J. C., Webster, R. G.: Evidence for host-cell selection of influenza virus antigenic variants. Nature303, 706–709 (1983).

    Google Scholar 

  29. Skehel, J. J., Waterfield, M. D.: Studies on the primary structure of the influenza virus hemagglutinin. Proc. Natl. Acad. Sci. U.S.A.72, 93–97 (1975).

    Google Scholar 

  30. Skehel, J. J., Bayley, P. M., Brown, E. B., Martin, S. R., Waterfield, M. D., White, J. M., Wilson, I. A., Wiley, D. C.: Changes in the conformation of the influenza virus hemagglutinin at the pH optimum of virus mediated membrane fusion. Proc. Natl. Acad. Sci. U.S.A.79, 968–972 (1982).

    Google Scholar 

  31. Vaananen, P., Kaariainen, L.: Fusion and haemolysis of erythrocytes caused by three togaviruses: semliki forest virus, sindbis and rubella. J. gen. Virol.46, 467–475 (1980).

    Google Scholar 

  32. Verhoeyen, M., Fang, R., Min Jou, W., Devos, R., Huylebroeck, D., Samon, E., Fiers, W.: Antigenic drift between the haemagglutinin of the Hong Kong influenza strains A/Aichi/2/68 and A/Victoria/3/75. Nature286, 771–776 (1980).

    Google Scholar 

  33. Verhoeyen, M., Van Rompuy, L., Min Jou, W., Huylebroeck, D., Fiers, W.: Complete nucleotide sequence of the B/Singapore/222/79 virus hemagglutinin gene and comparison with the B/Lee/40 hemagglutinin. Nucl. Acids Res.11, 4703–4712 (1983).

    Google Scholar 

  34. Webster, R. G., Brown, L. E., Jackson, D. C.: Changes in the antigenicity of the hemagglutinin molecule of H3 influenza virus at acidic pH. Virology126, 587–599 (1983).

    Google Scholar 

  35. White, J., Helenius, A.: pH dependent fusion between semliki forest virus membrane and liposomes. Proc. Natl. Acad. Sci. U.S.A.77, 3273–3277 (1980).

    Google Scholar 

  36. White, J., Helenius, A., Gething, M.-J.: Haemagglutinin of influenza virus expressed from a cloned gene promotes membrane fusion. Nature300, 658–659 (1982).

    Google Scholar 

  37. Wilson, I. A., Skehel, J. J., Wiley, D. C.: Structure of the haemagglutinin membrane protein of influenza virus at 3 Å resolution. Nature289, 366–373 (1981).

    Google Scholar 

  38. Winter, G., Fields, S., Brownlee, G. G.: Nucleotide sequence of the haemagglutinin gene of a human influenza virus H1 subtype. Nature292, 72–75 (1981).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

With 5 Figures

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruigrok, R.W.H., Cremers, A.F.M., Beyer, W.E.P. et al. Changes in the morphology of influenza particles induced at low pH. Archives of Virology 82, 181–194 (1984). https://doi.org/10.1007/BF01311162

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01311162

Keywords

Navigation