Attenuation of tick-borne encephalitis virus using large-scale random codon re-encoding

PLoS Pathogens
Lauriane De FabritusXavier de Lamballerie

Abstract

Large-scale codon re-encoding (i.e. introduction of a large number of synonymous mutations) is a novel method of generating attenuated viruses. Here, it was applied to the pathogenic flavivirus, tick-borne encephalitis virus (TBEV) which causes febrile illness and encephalitis in humans in forested regions of Europe and Asia. Using an infectious clone of the Oshima 5-10 strain ("wild-type virus"), a cassette of 1.4kb located in the NS5 coding region, was modified by randomly introducing 273 synonymous mutations ("re-encoded virus"). Whilst the in cellulo replicative fitness of the re-encoded virus was only slightly reduced, the re-encoded virus displayed an attenuated phenotype in a laboratory mouse model of non-lethal encephalitis. Following intra-peritoneal inoculation of either 2.105 or 2.106 TCID50 of virus, the frequency of viraemia, neurovirulence (measured using weight loss and appearance of symptoms) and neuroinvasiveness (detection of virus in the brain) were significantly decreased when compared with the wild-type virus. Mice infected by wild-type or re-encoded viruses produced comparable amounts of neutralising antibodies and results of challenge experiments demonstrated that mice previously infected with the re-enco...Continue Reading

References

Aug 1, 1997·Journal of Clinical Microbiology·I TakashimaN Hashimoto
Mar 12, 1998·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·J TomazicB Zakotnik
Feb 1, 2000·Zentralblatt Für Bakteriologie : International Journal of Medical Microbiology·E I Korenberg, Y V Kovalevskii
Jan 19, 2002·Annals of the New York Academy of Sciences·A D Barrett
Mar 5, 2003·Antiviral Research·T S GritsunE A Gould
May 28, 2003·Journal of Virology·Christopher T JonesRichard J Kuhn
Dec 4, 2003·Journal of Virology·Bimmi ShresthaMichael S Diamond
Mar 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Swaine L ChenHarley H McAdams
Apr 24, 2004·The Journal of General Virology·Caroline ThurnerPeter F Stadler
Dec 21, 2004·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·R N CharrelX de Lamballerie
Apr 6, 2006·Vector Borne and Zoonotic Diseases·Valentina N BakhvalovaOlga V Morozova
Dec 6, 2006·Immunology and Cell Biology·Nicholas J C KingAlison M Kesson
Feb 12, 2008·Lancet·E A Gould, T Solomon
Jun 28, 2008·Science·J Robert ColemanSteffen Mueller
Nov 21, 2008·The New England Journal of Medicine·John M Coffin
Dec 17, 2008·Virology·Daniel RůzekLibor Grubhoffer
Mar 7, 2009·The Journal of General Virology·Daniel RůzekLibor Grubhoffer
May 29, 2009·Journal of Medical Virology·Bersabeh TigabuMichael R Holbrook
Aug 8, 2009·Nature·Joseph M WattsKevin M Weeks
Apr 29, 2010·Veterinary Research Communications·Jian-Hua ZhouYong-Sheng Liu
Jun 15, 2010·Nature Biotechnology·Steffen MuellerEckard Wimmer
Oct 27, 2010·Proceedings of the National Academy of Sciences of the United States of America·Cristina GhergheKevin M Weeks
Oct 5, 2011·Euro Surveillance : Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin·A LundkvistM Hjertqvist
Apr 26, 2012·Molecular Biology and Evolution·J J BullC O Wilke
Apr 27, 2012·The Journal of General Virology·Andrew E Firth, Ian Brierley
Jun 12, 2012·Vaccine·Franz X Heinz, Karin Stiasny
Sep 25, 2011·Journal of Bioterrorism & Biodefense·Monica A McArthur, Michael R Holbrook
Nov 8, 2012·Knee Surgery, Sports Traumatology, Arthroscopy : Official Journal of the ESSKA·Jon KarlssonNeil P Thomas

❮ Previous
Next ❯

Citations

Jul 17, 2015·International Journal of Molecular Medicine·Julian Banerji
Dec 10, 2015·Trends in Microbiology·Miguel Angel MartínezMaria Nevot
Mar 22, 2018·Emerging Microbes & Infections·Jean-Sélim DriouichAntoine Nougairède
Jun 8, 2018·Journal of Virology·Maria NevotMiguel Angel Martinez
Feb 3, 2018·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Vincent P Mauro
Jul 4, 2019·Critical Reviews in Microbiology·Aurélie VelaySamira Fafi-Kremer
Oct 5, 2019·Nucleic Acids Research·Miguel Angel MartínezMaria Nevot
May 31, 2018·Scientific Reports·Alexander KulaCatherine Putonti
Aug 19, 2020·Vaccines·Mareike KubinskiGuus F Rimmelzwaan
Oct 13, 2020·Genome Biology and Evolution·James T Van LeuvenCraig R Miller
Apr 3, 2021·Frontiers in Microbiology·Ana Jordan-PaizMiguel Angel Martínez

❮ Previous
Next ❯

Datasets Mentioned

BETA
KF623542
AB062063

Methods Mentioned

BETA
transfection
ELISA
PCR

Software Mentioned

Codon W
CodonW
SPSS
GenScript

Related Concepts

Related Feeds

Bacteriophage: Phage Therapy

Phage therapy uses bacterial viruses (bacteriophages) to treat bacterial infections and is widely being recognized as an alternative to antibiotics. Here is the latest research.