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.

马立克病是全球家禽健康面临的主要灾难。该病由高度传染的马立克病病毒（MDV）引起，MDV属于疱疹病毒科。本研究揭示，与疱疹病毒科其他成员类似，MDV亦展现出复杂的剪接事件图谱，其中大部分剪接事件尚未被鉴定或注释。令人印象深刻的是，尽管这一事实的生物学意义尚不清楚，我们发现，尽管考虑到的毒株——致病性RB-1B和疫苗株CVI-988——序列相似性紧密，但众多病毒剪接异构体仍表现出株特异性。我们通过设计一种基于某些RNA物种存在的检测方法，在鸡胚成纤维细胞中区分由这两种毒株引起的感染，从而验证了我们的发现。据我们所知，本研究首次实现了这一结果，凸显了全面了解病毒转录组对于理解病毒致病机制的重要性。