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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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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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