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Molecular characterization of a reassortant virus derived from Lassa and Mopeia viruses

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Abstract

In this article we describe two new complete genomic sequences of Old World Arenaviruses: the Mopeia (MOP) virus and the reassortant MOP/LAS virus, clone 29, or ML29. This reassortant has the large (L) RNA from MOP virus and the small (S) RNA from Lassa (LAS) virus, Josiah strain. Recent studies showed that the ML29 virus is not pathogenic for mice, guinea pigs, or macaques, can completely protect guinea pigs from Lassa virus, and elicit vigorous cell-mediated immunity in immunized monkeys (Lukashevich, I. S., Patterson, J., Carrion, R., Moshkoff, D., Ticer, A., Zapata, J., Brasky, K., Geiger, R., Hubbard, G. B., Bryant, J., and Salvato, M. S., J Virol 79, 13934–13942, 2005). This is a molecular characterization of a reassortant virus, which has been put forward as a live attenuated vaccine candidate against Lassa Fever. Sequence analysis of this reassortant virus revealed 5 non-conservative amino acid substitutions that distinguished it from the parental LAS and MOP viruses. Three substitutions were found outside the conserved RNA-dependent RNA polymerase (RdRp) motifs. A fourth substitution was located between the glycoprotein (GPC)-cleavage site and the putative fusion peptide of GP2. The nucleocapsid protein (NP) contained a fifth substitution in the carboxyl-terminal region of the protein. Two mutations were found within each non-coding terminus of the L segment and one mutation was located in the 3′ non-coding region of the S segment of the MOP/LAS virus. ML29 mutations in its genomic termini may have implications for the genetic stability and replication efficiency of ML29 reassortant.

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Acknowledgments

The authors wish to thanks Dr. Robert Powell for excellent assistance in BSL3 laboratory, Dr. C. David Pauza for comprehensive discussion of results and Dr. Lisa Sadzewicz for clone sequencing assistance. This work was supported by NIH grants R21-AI52367, RO1-AI52367 and Middle Atlantic Regional Center of Excellence (MARCE) in Biodefense and Emerging Infectious Diseases Research to Dr. Igor S. Lukashevich.

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Authors and Affiliations

  1. Institute of Human Virology, University of Maryland Biotechnology Institute, 725 West Lombard Street, Baltimore, MD, 21201, USA

    Dmitry A. Moshkoff, Maria S. Salvato & Igor S. Lukashevich

Authors
  1. Dmitry A. Moshkoff
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  2. Maria S. Salvato
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  3. Igor S. Lukashevich
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Correspondence to Igor S. Lukashevich.

Additional information

The nucleotide sequence data for the of the S and L RNAs of the ML29 and Mopeia virus strains reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers: NC_006572-75.

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Moshkoff, D.A., Salvato, M.S. & Lukashevich, I.S. Molecular characterization of a reassortant virus derived from Lassa and Mopeia viruses. Virus Genes 34, 169–176 (2007). https://doi.org/10.1007/s11262-006-0050-3

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