Characterization of BoHV-4 ORF45

Bovine herpesvirus 4 BoHV4 is a Gammaherpesvirus of the genus Rhadinovirus. BoHV-4 infection is not associated to a specific disease. Genome structure and genes are well conserved in Gammaherpesvirus, and orf45 gene and its product, ORF45, is one of those. BoHV4 ORF45, has been suggested to be a tegument protein, however, BoHV4 ORF45 structure and function have not yet been experimentally characterized. In the present study, it was shown that BoHV-4 ORF45, is a phosphoprotein and localizes in the host cell nuclei. Through the generation of an ORF45-null mutant BoHV4 and its pararevertant, it was possible to demonstrate that ORF45 is essential for BoHV4 lytic replication and is associated to the viral particles. The impact of BoHV-4 ORF45 on cellular transcriptome was investigated, an aspect poorly explored or not at all for other Gammaherpesvirus. Many cellular transcriptional pathways were found to be alterate, mainly those involving p90 ribosomal S6 kinase RSK and signal-regulated kinase ERK complex, thus highlighting the authentic character of BoHV-4 ORF45 and paving the way to further investigations.