title: Large-scale recoding of an arbovirus genome to rebalance its insect versus mammalian preference.
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.
authors.affiliation: Department of Molecular Genetics and Microbiology and.
authors.forename: Sam H
authors.initials: SH
authors.lastname: Shen
authors.affiliation: Department of Molecular Genetics and Microbiology and Codagenix Inc., Stony Brook, NY 11794.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Stauft
authors.affiliation: Department of Molecular Genetics and Microbiology and.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Gorbatsevych
authors.affiliation: Department of Molecular Genetics and Microbiology and.
authors.forename: Yutong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Computer Science, Stony Brook University School of Medicine, Stony Brook, NY 11794; and.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Ward
authors.affiliation: Department of Molecular Genetics and Microbiology and.
authors.forename: Alisa
authors.initials: A
authors.lastname: Yurovsky
authors.affiliation: Department of Molecular Genetics and Microbiology and Codagenix Inc., Stony Brook, NY 11794.
authors.forename: Steffen
authors.initials: S
authors.lastname: Mueller
authors.affiliation: Department of Molecular Genetics and Microbiology and.
authors.forename: Bruce
authors.initials: B
authors.lastname: Futcher
authors.affiliation: Department of Molecular Genetics and Microbiology and Codagenix Inc., Stony Brook, NY 11794 Eckard.Wimmer@stonybrook.edu.
authors.forename: Eckard
authors.initials: E
authors.lastname: Wimmer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000276:immunology; D001103:Arboviruses / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003062:Codon; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D007303:Insect Vectors / Q000166:cytology / Q000235:genetics / Q000821:virology*; D008322:Mammals / Q000235:genetics / Q000821:virology*; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D020365:RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000276:immunology; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology / Q000821:virology; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000914:Antibodies, Viral; D003062:Codon; D020365:RNA Helicases; D012697:Serine Endopeptidases; D014613:Vaccines, Attenuated; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: arbovirus; codon pair bias; dengue; vaccine
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