Reference : Bovine herpesvirus 4 ORF73 is dispensable for viral growth in vitro but is essential ...
Scientific journals : Article
Life sciences : Veterinary medicine & animal health
Bovine herpesvirus 4 ORF73 is dispensable for viral growth in vitro but is essential for viral persistence in vivo.
Thirion, M. [> > > >]
Machiels, Bénédicte mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Farnir, Frédéric mailto [Université de Liège - ULiège > Département de productions animales > Biostatistiques et bioinformatique appliquées aux sc. vétér. >]
Donofrio, G. [> > > >]
Gillet, Laurent mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Dewals, Benjamin G mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Vanderplasschen, Alain mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Journal of General Virology (The)
Society for General Microbiology
Yes (verified by ORBi)
United Kingdom
[en] Animals ; Antibodies, Viral/blood ; Disease Models, Animal ; Gene Deletion ; Herpesviridae Infections/virology ; Herpesvirus 4, Bovine/genetics/growth & development/pathogenicity/physiology ; Rabbits ; Viral Proteins/genetics/physiology ; Virulence ; Virulence Factors/genetics/physiology ; Virus Latency ; Virus Replication
[en] ORF73 orthologues encoded by different rhadinoviruses have been studied extensively. These studies revealed that the ORF73 expression product (pORF73) is a multifunctional protein essential for latency that enables episome tethering to mitotic chromosomes and modulates cellular pathways implicated in growth and survival of latently infected cells. Comparison of pORF73 orthologues encoded by rhadinoviruses reveals important variations in amino acid sequence length and composition. Bovine herpesvirus 4 (BoHV-4) encodes by far the shortest ORF73 orthologue with a size equivalent to only 22% of the largest orthologues. The present study focused on determining if BoHV 4 ORF73 is a bona fide gene and investigating whether it is essential for latency as established for larger ORF73 orthologues. Our results demonstrate that BoHV-4 ORF73 is transcribed as immediate-early bicistronic mRNA together with ORF71. Using a BoHV-4 bacterial artificial chromosome clone, we produced a strain deleted for ORF73 and a revertant strain. Deletion of BoHV-4 ORF73 did not affect the capacity of the virus to replicate in vitro, but it prevented latent infection in vivo using a rabbit model. Interestingly, the strain deleted for ORF73 induced an anti-BoHV-4 humoral immune response comparable to that elicited by wild-type and revertant recombinants. Together, these results demonstrate that despite its relatively small size, BoHV-4 ORF73 is a functional homologue of larger rhadinovirus ORF73 orthologues, and highlight the potential of ORF73 deletion for the development of BoHV-4 as a vector in vaccinology.

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