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Lassa Virus Reverse Genetics

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Reverse Genetics of RNA Viruses

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1602))

Abstract

The Old World (OW) arenavirus Lassa (LASV ) is estimated to infect several hundred thousand people yearly in West Africa, resulting in high numbers of Lassa fever (LF), a viral hemorrhagic fever (HF) disease associated with high morbidity and mortality. To date, no licensed vaccines are available to LASV infections, and anti-LASV drug therapy is limited to an off-label use of ribavirin (Rib) that is only partially effective. The development of reverse genetics has provided investigators with a novel and powerful approach for the investigation of the molecular, cell biology, and pathogenesis of LASV. The use of cell-based LASV minigenome (MG) systems has allowed examining the cis- and trans-acting factors involved in genome replication and gene transcription and the identification of novel drugable LASV targets. Likewise, it is now feasible to rescue infectious recombinant (r)LASV entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify antiviral drugs against LASV and the implementation of novel strategies to develop live-attenuated vaccines (LAV). In this chapter we will summarize the state-of-the-art experimental procedures for implementation of LASV reverse genetics. In addition, we will briefly discuss some significant translational research developments that have been made possible upon the development of LASV reverse genetics.

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Acknowledgments

LASV research in L. M-S laboratory was funded by the NIH grant 1R21AI119775-01 and by the University of Rochester Drug Discovery Pilot Award Program.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Rochester, 601 Elmwood Avenue Box 672, Rochester, NY, 14642, USA

    Luis Martínez-Sobrido

  2. University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555, USA

    Slobodan Paessler

  3. Department of Immunology and Microbial Science, The Scripps Research Institute, Scripps Clinic South Driveway, La Jolla, CA, 92037, USA

    Juan Carlos de la Torre

Authors
  1. Luis Martínez-Sobrido
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  2. Slobodan Paessler
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  3. Juan Carlos de la Torre
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Corresponding authors

Correspondence to Luis Martínez-Sobrido or Juan Carlos de la Torre .

Editor information

Editors and Affiliations

  1. Department of Population Health, Poultry Diagnostic and Research Center, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA

    Daniel R. Perez

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Martínez-Sobrido, L., Paessler, S., de la Torre, J.C. (2017). Lassa Virus Reverse Genetics. In: Perez, D. (eds) Reverse Genetics of RNA Viruses. Methods in Molecular Biology, vol 1602. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6964-7_13

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  • DOI: https://doi.org/10.1007/978-1-4939-6964-7_13

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6962-3

  • Online ISBN: 978-1-4939-6964-7

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