期刊
PLOS ONE
卷 11, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0159564
关键词
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资金
- French Agence Nationale de la Recherche [ANR-14-CE14-0001]
- PREDEMICS (European Union Seventh Framework Programme) [278433]
- European Virus Archive goes global programme (EVAg
- European Union - Horizon programme) [653316]
- Agence Nationale de la Recherche (ANR) [ANR-14-CE14-0001] Funding Source: Agence Nationale de la Recherche (ANR)
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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