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

• DOI: 10.1073/pnas.1502864112
• Publication Date: 2015-04-01T09:46:36Z
• Authors: Sam H. Shen; Charles B. Stauft; Oleksandr Gorbats...; Yutong Song; Charles B. Ward; Alisa Yurovsky; Steffen Mueller; Bruce Futcher; Eckard Wimmer
• Keywords: Arthropod; Arbovirus Infections; Human pathogen

Significance Arboviruses (arthropod-borne viruses), a large group of RNA viruses, replicate in insects that transmit them to mammals, their second host. Insects and mammals have evolved different protein encoding strategies (codon pair bias); hence, arboviruses must delicately balance encodings between two phyla. Using dengue virus (DENV), the most important human arbovirus pathogen, as model, we have, by computer design chemical synthesis, undone this codon bias favor insects. Recoded DENVs grow well insect cells but are highly attenuated mammalian suckling mice. This unique approach offers previously unidentified possibility rapidly develop new vaccine candidates against DENV perhaps many arboviruses.