Characterization of BoHV-4 ORF45

Bovine herpesvirus 4 (BoHV-4) is a Gammaherpesvirus belonging to theRhadinovirus genus. The bovine is BoHV-4's natural host, and the African bu?alois BoHV-4's natural reservoir. In any case, BoHV-4 infection is not associatedwith a specific disease. Genome structure and genes are well-conserved inGammaherpesvirus, and the orf45 gene and its product, ORF45, are one ofthose. BoHV-4 ORF45 has been suggested to be a tegument protein; however,its structure and function have not yet been experimentally characterized. Thepresent study shows that BoHV-4 ORF45, despite its poor homology withother characterized Rhadinovirus ORF45s, is structurally related to Kaposi'ssarcoma-associated herpesvirus (KSHV), is a phosphoprotein, and localizes inthe host cell nuclei. Through the generation of an ORF45-null mutant BoHV-4and its pararevertant, it was possible to demonstrate that ORF45 is essential forBoHV-4 lytic replication and is associated with the viral particles, as for the othercharacterized Rhadinovirus ORF45s. Finally, the impact of BoHV-4 ORF45 oncellular transcriptome was investigated, an aspect poorly explored or not at allfor other Gammaherpesvirus. Many cellular transcriptional pathways were foundto be altered, mainly those involving p90 ribosomal S6 kinase (RSK) and signal-regulated kinase (ERK) complex (RSK/ERK). It was concluded that BoHV-4 ORF45has similar characteristics to those of KSHV ORF45, and its unique and incisiveimpact on the cell transcriptome paves the way for further investigations.