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Molecular analysis of the virulence attenuation process in Junín virus vaccine genealogy

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Abstract

The Junín virus strain Candid#1 was developed as a live attenuated vaccine for Argentine hemorrhagic fever. In this article, we report sequence information of the L and S RNAs of Junín virus Candid#1 and XJ#44 strains, and show the comparisons with the XJ13 wild-type strain and with other Junín virus strains, like Romero, IV4454 and MC2 strains, and other closely and distantly related arenaviruses. Comparisons of the nucleotide and amino acid sequences of all genes of three strains from the same vaccine genealogy, revealed different point mutations that could be associated with the attenuated phenotype. A 91% of the mutations found are consistent with a hypothesis of progressive attenuation of virulence from XJ13 to XJ#44 and to Candid#1; 39% of mutations were observed in XJ#44 and conserved in Candid#1, while another 52% of the mutations appeared only in Candid#1 strain. The remaining 9% corresponded to reverse mutations in the L gene. In summary, the present work shows a set of mutations that could be related to the virulence attenuation phenomenon. This information will serve as a starting point to study this biological phenomenon, provided that a reverse genetics system for Junín virus is developed to allow the generation of infectious virions with specific mutations.

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References

  1. J.C.S. Clegg, M.D. Bowen, M.J. Buchmeier, J-P. Gonzalez, I.S. Lukashevich, C.J. Peters, R. Rico-Hesse, V. Romanowski. Arenaviridae, in Virus Taxonomy. Seventh Report of the International Committee on Taxonomy of Viruses, ed. by M.H.V. van Regenmortel, C.M. Fauquet, D.H.L. Bishop, E.B. Carstens, M.K. Estes, S.M. Lemon, J. Maniliff, M.A. Mayo, D.J. McGeoch, C.R. Pringle, R. B. Wickner (Academic Press, New York, 2000), pp. 633–640

  2. C.A. Tidona, G. Darai, The Springer Index of Viruses (Springer, New York, 2001)

    Google Scholar 

  3. D.A. Enria, A.M. Briggiler, Z. Sanchez, Antiviral Res. 78(1), 132–139 (2008)

    Article  CAS  PubMed  Google Scholar 

  4. T. Strecker, R. Eichler, J. van der Meulen, W. Weissenhorn, H.D. Klenk, W. Garten, O. Lenz, J. Virol. 77(23), 12927 (2003)

    Article  CAS  Google Scholar 

  5. M. Perez, D.L. Greenwald, J.C. deLa Torre, J. Virol. 78(20), 11443–11448 (2004)

    Article  CAS  PubMed  Google Scholar 

  6. R.N. Charrel, X. de Lamballerie, S. Emonet, Curr. Opin. Micribiol. 11, 362–368 (2008)

    Article  Google Scholar 

  7. J.C. de la Torre, Antiviral Res. 80(3), 239–250 (2008)

    Article  PubMed  Google Scholar 

  8. S.E. Goñi, J.A. Iserte, A.M. Ambrosio, V. Romanowski, P.D. Ghiringhelli, M.E. Lozano, Virus Genes 32, 37–41 (2006)

    Article  PubMed  Google Scholar 

  9. A.M. Ambrosio, M.C. Saavedra, L.M. Riera, R.M. Fassio, Acta Bioquím. Clín. Lat. 40(1), 5–17 (2006). (ISSN 0325-2957)

    Google Scholar 

  10. D. Enría, J.G. Barrera Oro, Curr. Top. Microbiol. Immunol. 263, 239–261 (2002)

    PubMed  Google Scholar 

  11. A.S. Parodi, D.J. Greenway, H.R. Rugiero, E. Rivero, M.J. Frigerio, N.E. Mettler, F. Garzon, M. Boxaca, L.B. Guerrero, N.R. Nota, Día Médico (Buenos Aires) 30, 2300–2302 (1958)

    CAS  Google Scholar 

  12. J.D. Thompson, T.J. Gibson, F. Plewniak, F. Jeanmougin, D.G. Higgins, Nucleic Acids Res. 25, 4876–4882 (1997)

    Article  CAS  PubMed  Google Scholar 

  13. M. Zuker, Nucleic Acids Res. 31(13), 3406–3415 (2003)

    Article  CAS  PubMed  Google Scholar 

  14. E. Gasteiger, A. Gattiker, C. Hoogland, I. Ivanyi, R.D. Appel, A. Bairoch, Nucleic Acids Res. 31, 3784–3788 (2003)

    Article  CAS  PubMed  Google Scholar 

  15. R. Gupta, E. Jung, S. Brunak, Prediction of N-glycosylation sites in human proteins, in preparation (2004) (available at: http://www.cbs.dtu.dk/services/NetNGlyc/)

  16. B.C. Schaefer, Anal. Biochem. 227, 255–273 (1995)

    Article  CAS  PubMed  Google Scholar 

  17. K.T. McKee Jr., B.G. Mahlandt, J.I. Maiztegui, G.A. Eddy, C.J. Peters, J. Infect. Dis. 152, 218–221 (1985)

    PubMed  Google Scholar 

  18. N.E. Yun, N.S. Linde, N. Dziuba, M.A. Zacks, J.N. Smith, J.K. Smith, J.F. Aronson, O.V. Chumakova, H.M. Lander, C.J. Peters, S. Paessler, Am. J. Trop. Med. Hyg. 79(2), 275–282 (2008)

    PubMed  Google Scholar 

  19. M.I. Berría, L.F. Gutman Frugone, R. Girda, J.G. Barrera Oro, Medicina (Buenos Aires) 27, 93–98 (1967)

    Google Scholar 

  20. N.A. Candurra, E.B. Damonte, C.E. Coto, J. Med. Virol. 27, 145 (1989)

    Article  CAS  PubMed  Google Scholar 

  21. M.C. Weissenbacher, R.P. Laguens, C.E. Coto, Curr. Top. Microbiol. Inmunol. 134, 79–116 (1987)

    CAS  Google Scholar 

  22. S.J. Polyak, S. Zheng, D.G. Harnish, J. Virol. 69(5), 3211–3215 (1995)

    CAS  PubMed  Google Scholar 

  23. M.L. Flanagan, J. Oldenburg, T. Reignier, N. Holt, G.A. Hamilton, V.K. Martin, P.M. Cannon, J. Virol. 82(2), 938–948 (2008)

    Article  CAS  PubMed  Google Scholar 

  24. S. Vieth, A.E. Torda, M. Asper, H. Schmitz, S. Günter, Virology 318, 153–168 (2004)

    Article  CAS  PubMed  Google Scholar 

  25. S. Lan, L. McLay, J. Aronson, H. Ly, Y. Liang, Arch. Virol. 153(7), 1241–1250 (2008)

    Article  CAS  PubMed  Google Scholar 

  26. M.J. Endres, C. Griot, F. Gonzalez-Scarano, N. Nathanson, J. Virol. 65, 5465–5470 (1991)

    CAS  PubMed  Google Scholar 

  27. Y. Riviere, R. Ahmed, P.J. Southern, M.J. Buchmeier, M.B.A. Oldstone, J. Virol. 55, 704–709 (1985)

    CAS  PubMed  Google Scholar 

  28. M.A. Tortorici, P.D. Ghiringhelli, M.E. Lozano, C.G. Albariño, V. Romanowski, J. Gen. Virol. 82, 121–128 (2001)

    CAS  PubMed  Google Scholar 

  29. A.A. Capul, M. Perez, E. Burke, S. Kunz, M.J. Buchmeier, J.C. de la Torre, J. Virol. 81(17), 9451–9460 (2007)

    Article  CAS  PubMed  Google Scholar 

  30. J. York, V. Romanowski, M. Lu, J.H. Nunberg, J. Virol. 78(19), 10783–10792 (2004)

    Article  CAS  PubMed  Google Scholar 

  31. S.M. Wilson, J.C.S. Clegg, Virology 180, 543–552 (1991)

    Article  CAS  PubMed  Google Scholar 

  32. M.T. Franze-Fernandez, S. Iapalucci, N. Lopez, C. Rossi, in The Arenaviridae, ed. by M.S. Salvato (Plenum Press, New York, 1993), pp. 113–132

    Google Scholar 

  33. M.A. Tortorici, C.G. Albariño, D.M. Posik, P.D. Ghiringhelli, M.E. Lozano, R.V. Rivera Pomar, V. Romanowski, Virus Res. 73, 41–55 (2001)

    Article  CAS  PubMed  Google Scholar 

  34. D. Garcin, D. Kolakofsky, J. Virol. 66(3), 1370–1376 (1992)

    CAS  PubMed  Google Scholar 

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Acknowledgments

We are very grateful to Dr. J. G. Barrera Oro from USAMRJID (Frederick, Maryland, USA) who provided us with a XJ#44 seed, to Dr. Ana María Ambrosio and Dr. María del Carmen Saavedra who prepare Candid#1 virions and Dr. Diego Golombek who carefully read this manuscript. This work was supported by PICT 38138 from ANPCYT and PIP 5813 from CONICET (Argentina). S. E. Goñi, B. I. Stephan, and C. S. Borio have a research fellowship from CONICET, J. A. Iserte holds a research fellowship from ANPCYT, P. D. Ghiringhelli and M. E. Lozano are members of the research career of CONICET.

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Correspondence to Mario Enrique Lozano.

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Goñi, S.E., Iserte, J.A., Stephan, B.I. et al. Molecular analysis of the virulence attenuation process in Junín virus vaccine genealogy. Virus Genes 40, 320–328 (2010). https://doi.org/10.1007/s11262-010-0450-2

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  • DOI: https://doi.org/10.1007/s11262-010-0450-2

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