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Generation and Comparative Genomics of Synthetic Dengue Viruses

  • Eli Goz
  • Yael Tsalenchuck
  • Rony Oren Benaroya
  • Shimshi Atar
  • Tahel Altman
  • Justin Julander
  • Tamir TullerEmail author
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 10562)

Abstract

Synthetic virology is an important multidisciplinary scientific field, with emerging applications in biotechnology and medicine, aiming at developing methods to generate and engineer synthetic viruses. Here we demonstrate a full multidisciplinary pipeline for generation and analysis of synthetic RNA viruses and specifically apply it to Dengue virus type 2 (DENV-2). The major steps of the pipeline include comparative genomics of endogenous and synthetic viral strains. In particular, we show that although the synthetic DENV-2 viruses were found to have lower nucleotide variability, their phenotype, as reflected in the study of the AG129 mouse model morbidity, RNA levels, and neutralization antibodies, is similar or even more pathogenic in comparison to the wildtype master strain. These results may suggest that synthetic DENV-2 may enhance virulence if the correct sequence is selected. The approach reported here can be used for understanding the functionality and the fitness effects of any set of mutations in viral RNA. It can be also used for editing RNA viruses for various target applications.

Notes

Acknowledgment

E.G. is supported, in part, by a fellowship from the Edmond J. Safra Center for Bioinformatics at Tel-Aviv University. T.T. is partially supported by the Minerva ARCHES award.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Eli Goz
    • 1
    • 2
  • Yael Tsalenchuck
    • 2
  • Rony Oren Benaroya
    • 2
  • Shimshi Atar
    • 1
  • Tahel Altman
    • 2
  • Justin Julander
    • 3
  • Tamir Tuller
    • 1
    • 2
    • 4
    Email author
  1. 1.Department of Biomedical EngineeringTel-Aviv UniversityRamat AvivIsrael
  2. 2.SynVaccine Ltd.Tel AvivIsrael
  3. 3.Institute for Antiviral ResearchUtah State UniversityLoganUSA
  4. 4.Sagol School of NeuroscienceTel-Aviv UniversityRamat AvivIsrael

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