Pervasive differential splicing in Marek’s Disease Virus can discriminate CVI-988 vaccine strain from RB-1B virulent strain in chicken embryonic fibroblasts

Marek’s disease is a major scourge challenging poultry health worldwide. It is caused by the highly contagious Marek’s disease virus (MDV), an alphaherpesvirus. Here we show that, similar to other members of its Herpesviridae family, MDV also presents a complex landscape of splicing events, most of which are uncharacterised and/or not annotated. Quite strikingly, and although the biological relevance of this fact is unknown, we found that a number of viral splicing isoforms are strain-specific despite the close sequence similarity of the strains considered, virulent RB-1B and vaccine CVI-988. We validated our findings by devising an assay that discriminates infections caused by the two strains in chicken embryonic fibroblasts based on the presence of some RNA species. To our knowledge, this study is the first ever to accomplish such a result, emphasizing how important a comprehensive knowledge of the viral transcriptome can be to understand viral pathogenesis.