An Epstein-Barr virus mutant produces immunogenic defective particles devoid of viral DNA.
Fiche publication
Date publication
février 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr DELECLUSE Henri-Jacques
Tous les auteurs :
Pavlova S, Feederle R, Gartner K, Fuchs W, Granzow H, Delecluse HJ
Lien Pubmed
Résumé
Virus-like particles (VLPs) from hepatitis B and human papillomaviruses have been successfully used as preventative vaccines against these infectious agents. These VLPs consist of a self-associating capsid polymer formed from a single structure protein and are devoid of viral DNA. Since virions from herpesviruses consist of a large number of molecules of viral and cellular origin, generating VLPs from a subset of these would be a particularly arduous task. Therefore, we have adopted an alternative strategy that consists of producing DNA-free defective virus particles in a cell line infected by a herpesvirus mutant incapable of packaging DNA. We previously reported that an Epstein-Barr virus (EBV) mutant devoid of the terminal repeats (DeltaTR) that act as packaging signals in herpesviruses produces substantial amounts of VLPs and of light particles (LPs). However, DeltaTR virions retained some infectious genomes, and although these mutants had lost their transforming abilities, this poses potential concerns for clinical applications. Therefore, we have constructed a series of mutants that lack proteins involved in maturation and assessed their ability to produce viral DNA-free VLP/LPs. Some of the introduced mutations were deleterious for capsid maturation and virus production. However, deletion of BFLF1/BFRF1A or of BBRF1 resulted in the production of DNA-free VLPs/LPs. The DeltaBFLF1/BFRF1A viruses elicited a potent CD4(+) T-cell response that was indistinguishable from the one obtained with wild-type controls. In summary, the defective particles produced by the DeltaBFLF1/BFRF1A mutant fulfill the criteria of efficacy and safety expected from a preventative vaccine.
Référence
J Virol. 2013 Feb;87(4):2011-22