%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A de Fabritus, L.
%A Nougairede, A.
%A Aubry, F.
%A Gould, E. A.
%A de Lamballerie, Xavier
%T Utilisation of ISA reverse genetics and large-scale random codon re-encoding to produce attenuated strains of tick-borne encephalitis virus within days
%D 2016
%L PAR00014994
%G ENG
%J Plos One
%@ 1932-6203
%M ISI:000381768400007
%N 8
%P e0159564 [11 ]
%R 10.1371/journal.pone.0159564
%U https://www.documentation.ird.fr/hor/PAR00014994
%V 11
%W Horizon (IRD)
%X Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.
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