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Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4749-54. doi: 10.1073/pnas.1502864112. Epub 2015 Mar 30.

Large-scale recoding of an arbovirus genome to rebalance its insect versus mammalian preference.

Author information

1
Department of Molecular Genetics and Microbiology and.
2
Department of Molecular Genetics and Microbiology and Codagenix Inc., Stony Brook, NY 11794.
3
Department of Computer Science, Stony Brook University School of Medicine, Stony Brook, NY 11794; and.
4
Department of Molecular Genetics and Microbiology and Codagenix Inc., Stony Brook, NY 11794 Eckard.Wimmer@stonybrook.edu.

Abstract

The protein synthesis machineries of two distinct phyla of the Animal kingdom, insects of Arthropoda and mammals of Chordata, have different preferences for how to best encode proteins. Nevertheless, arboviruses (arthropod-borne viruses) are capable of infecting both mammals and insects just like arboviruses that use insect vectors to infect plants. These organisms have evolved carefully balanced genomes that can efficiently use the translational machineries of different phyla, even if the phyla belong to different kingdoms. Using dengue virus as an example, we have undone the genome encoding balance and specifically shifted the encoding preference away from mammals. These mammalian-attenuated viruses grow to high titers in insect cells but low titers in mammalian cells, have dramatically increased LD50s in newborn mice, and induce high levels of protective antibodies. Recoded arboviruses with a bias toward phylum-specific expression could form the basis of a new generation of live attenuated vaccine candidates.

KEYWORDS:

arbovirus; codon pair bias; dengue; vaccine

PMID:
25825721
PMCID:
PMC4403163
DOI:
10.1073/pnas.1502864112
[Indexed for MEDLINE]
Free PMC Article

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