1887

Abstract

Alpha- and flaviviruses contain class II fusion proteins, which form ion-permeable pores in the target membrane during virus entry. The pores generated during entry of the alphavirus Semliki Forest virus have been shown previously to be blocked by lanthanide ions. Here, analyses of the influence of rare earth ions on the entry of the flaviviruses West Nile virus and Uganda S virus revealed an unexpected effect of lanthanide ions. The results showed that a 30 s treatment of cells with an appropriate lanthanide ion changed the cellular chemistry into a state in which the cells no longer supported the multiplication of flaviviruses. This change occurred in cells treated before, during or after infection, did not inhibit multiplication of Semliki Forest virus and did not interfere with host-cell multiplication. The change was generated in vertebrate and insect cells, and was elicited in the presence of actinomycin D. In vertebrate cells, the change was elicited specifically by La, Ce, Pr and Nd. In insect cells, additional lanthanide ions had this activity. Further analyses showed that lanthanide ion treatment blocked the ability of the host cell to support the replication of flavivirus RNA. These results open two areas of research: the study of molecular alterations induced by lanthanide ion treatment in uninfected cells and the analysis of the resulting modifications of the flavivirus RNA replicase complex. The findings possibly open the way for the development of a general chemotherapy against flavivirus diseases such as Dengue fever, Japanese encephalitis, West Nile fever and yellow fever.

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2007-11-01
2024-04-28
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References

  1. Boege U., Wengler G., Wengler G., Wittmann-Liebold B. 1980; Partial amino acid sequences of Sindbis and Semliki Forest virus-specific core proteins. Virology 103:178–190 [CrossRef]
    [Google Scholar]
  2. Burke D. S., Monath T. P. 2001; Flaviviruses. In Fields Virology , 4th edn. pp 1043–1125 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  3. Carrasco L. 1995; Modification of membrane permeability by animal viruses. Adv Virus Res 45:61–112
    [Google Scholar]
  4. Castle E., Leidner U., Nowak Th., Wengler G., Wengler G. 1986; Primary structure of the West Nile flavivirus genome region coding for all nonstructural proteins. Virology 149:10–26 [CrossRef]
    [Google Scholar]
  5. Koschinski A., Wengler G., Wengler G., Repp H. 2003; The membrane proteins of flaviviruses form ion-permeable pores in the target membrane after fusion: identification of the pores and analysis of their possible role in virus infection. J Gen Virol 84:1711–1721 [CrossRef]
    [Google Scholar]
  6. Koschinski A., Wengler G., Wengler G., Repp H. 2005; Rare earth ions block the ion pores generated by the class II fusion proteins of alphaviruses and allow analysis of the biological functions of these pores. J Gen Virol 86:3311–3320 [CrossRef]
    [Google Scholar]
  7. Lescar J., Roussel A., Wien M. W., Navaza J., Fuller S. D., Wengler G., Wengler G., Rey F. A. 2001; The fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH. Cell 105:137–148 [CrossRef]
    [Google Scholar]
  8. Leyssen P., Charlier N., Paeshuyse J., De Clerecq E., Neyts J. 2003; Prospects for antiviral therapy. Adv Virus Res 61:511–553
    [Google Scholar]
  9. Lindenbach B. D., Rice C. M. 2001; Flaviviridae : the viruses and their replication. In Fields Virology , 4th edn. pp 991–1041 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  10. Nyfeler S., Senn K., Kempf C. 2001; Expression of Semliki Forest virus E1 protein in Escherichia coli . J Biol Chem 276:15453–15457 [CrossRef]
    [Google Scholar]
  11. Paredes A. M., Ferreira D., Horton M., Saad A., Tsuruta H., Johnston R., Klimstra W., Ryman K., Hernandez R. other authors 2004; Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion. Virology 324:373–386 [CrossRef]
    [Google Scholar]
  12. Pletnev S. V., Zhang W., Mukhopadhyay S., Fisher B. R., Hernandez R., Brown D. T., Baker T. S., Rossmann M. G., Kuhn R. J. 2001; Locations of carbohydrate sites on alphavirus glycoproteins show that E1 forms an icosahedral scaffold. Cell 105:127–136 [CrossRef]
    [Google Scholar]
  13. Scherrer K. 1969; Isolation and sucrose gradient analysis of RNA. In Fundamental Techniques in Virology pp 413–432 Edited by Habel K., Salzman N. P. New York/London: Academic Press;
    [Google Scholar]
  14. Schlesinger S., Schlesinger M. J. 2001; Togaviridae : the viruses and their replication. In Fields Virology , 4th edn. pp 895–916 Edited by Knipe D. M., Howley P. M. Philadelphia, PA: Lippincott Williams & Wilkins;
    [Google Scholar]
  15. Singh K. R. P. 1967; Cell cultures derived from larvae of Aedes albopictus (Skuse) and Aedes aegypti (L.). Curr Sci 36:506–508
    [Google Scholar]
  16. Wengler G., Wengler G., Gross H. J. 1978; Studies in virus-specific nucleic acids synthesized in vertebrate and mosquito cells infected with flaviviruses. Virology 89:423–437 [CrossRef]
    [Google Scholar]
  17. Wengler G., Koschinski A., Wengler G., Dreyer F. 2003; Entry of alphaviruses at the plasma membrane converts the viral surface proteins into an ion-permeable pore that can be detected by electrophysiological analyses of whole-cell membrane currents. J Gen Virol 84:173–181 [CrossRef]
    [Google Scholar]
  18. White J., Kartenbeck J., Helenius A. 1980; Fusion of Semliki Forest virus with the plasma membrane can be induced by low pH. J Cell Biol 87:264–272 [CrossRef]
    [Google Scholar]
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