TY - GEN
T1 - Generation and comparative genomics of synthetic dengue viruses
AU - Goz, Eli
AU - Tsalenchuck, Yael
AU - Benaroya, Rony Oren
AU - Atar, Shimshi
AU - Altman, Tahel
AU - Julander, Justin
AU - Tuller, Tamir
N1 - Publisher Copyright:
© 2017, Springer International Publishing AG.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85030671458&partnerID=8YFLogxK
U2 - 10.1007/978-3-319-67979-2_3
DO - 10.1007/978-3-319-67979-2_3
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AN - SCOPUS:85030671458
SN - 9783319679785
T3 - Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
SP - 31
EP - 52
BT - Comparative Genomics - 15th International Workshop, RECOMB CG 2017, Proceedings
A2 - Nakhleh, Luay
A2 - Meidanis, Joao
PB - Springer Verlag
T2 - 15th International Workshop on Comparative Genomics, RECOMB CG 2017
Y2 - 4 October 2017 through 6 October 2017
ER -
