Characterization of BoHV-4 ORF45

Bovine herpesvirus 4 (BoHV-4) is a Gammaherpesvirus of the genus Rhadinovirus , his natural host is the bovine whereas the African Buffalo the natural reservoir. Anyhow, BoHV-4 infection is not associated to a specific disease. Genome structure and genes are well conserved in Gammaherpesvirus , and orf 45 gene and its product, ORF45, is one of those. BoHV-4 ORF45 has been suggested to be a tegument protein, however, BoHV-4 ORF45 structure and function have not yet been experimentally characterized. In the present study, it is shown that BoHV-4 ORF45, despite its poor homology with other characterized Rhadinovirus ORF45s, is structurally related to Kaposi’s sarcoma-associated herpesvirus (KSHV), is a phosphoprotein and localizes in the host cell nuclei. Through the generation of an ORF45-null mutant BoHV-4 and its pararevertant, it was possible to demonstrate that ORF45 is essential for BoHV-4 lytic replication and is associated to the viral particles, as for the other characterized Rhadinovirus ORF45s. Finally, 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 (RSK/ERK), thus highlighting the authentic character of BoHV-4 ORF45 and paving the way to further investigations. ### Competing Interest Statement The authors have declared no competing interest.