@article{PAR00014994,
  title = {{U}tilisation of {ISA} reverse genetics and large-scale random codon re-encoding to produce attenuated strains of tick-borne encephalitis virus within days},
  author = {de {F}abritus, {L}. and {N}ougairede, {A}. and {A}ubry, {F}. and {G}ould, {E}. {A}. and de {L}amballerie, {X}avier},
  editor = {},
  language = {{ENG}},
  abstract = {{L}arge-scale codon re-encoding is a new method of attenuating {RNA} viruses. {H}owever, the use of infectious clones to generate attenuated viruses has inherent technical problems. {W}e 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. {W}e produced wild-type ({WT}) and two re-encoded {TBEV}s, containing 273 or 273+284 synonymous mutations in the {NS}5 and {NS}5+{NS}3 coding regions respectively. {B}oth 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. {M}oreover, all infected animals produced neutralizing antibodies. {T}his novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.},
  keywords = {},
  booktitle = {},
  journal = {{P}los {O}ne},
  volume = {11},
  numero = {8},
  pages = {e0159564 [11 p.]},
  ISSN = {1932-6203},
  year = {2016},
  DOI = {10.1371/journal.pone.0159564},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00014994},
}