Location: Endemic Poultry Viral Diseases ResearchTitle: Pervasive differential splicing in Marek’s Disease Virus can discriminate CVI-988 vaccine strain from RB-1B virulent strain in chicken embryonic fibroblasts
|SADIGH, YASHAR - The Pirbright Institute|
|TAHIRI-ALAOUI, ABDESSAMAD - Jenner Institute|
|NAIR, VENUGOPAL - The Pirbright Institute|
|RIBECA, PAULO - The Pirbright Institute|
Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/10/2020
Publication Date: 3/18/2020
Citation: Sadigh, Y., Tahiri-Alaoui, A., Spatz, S.J., Nair, V., Ribeca, P. 2020. Pervasive differential splicing in Marek’s Disease Virus can discriminate CVI-988 vaccine strain from RB-1B virulent strain in chicken embryonic fibroblasts. Viruses. 12(3), 329. https://doi.org/10.3390/v12030329.
Interpretive Summary: Marek’s disease virus (MDV) causes an agro-economically important disease of chickens on a worldwide basis. Although commercial poultry are vaccinated against MDV, it is not possible to achieve sterilising immunity, and available vaccines can only protect chickens against the symptoms of the disease. Vaccinated chicken often become superinfected with virulent strains, shedding virus into the environment. The most efficacious of vaccine strains, CVI-988,shares >99% sequence identity with the prototype virulent virus RB-1B. Interestingly, our work shows that despite their almost identical sequences CVI-988 and RB-1B have significantly different splicing profiles. This discovery enabled us to design an assay capable of specifically detecting some splicing isoforms expressed by CVI-988 and absent in the RB-1B transcriptome. This next generation approach to differentiate strains of MDV will undoubtedly provide insight into the roles spliced transcripts play in the pathogenesis of MDV and its prevention
Technical Abstract: 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 splice isoforms are strain-specific. This biological insight enabled us to devise an assay that discriminates infections caused by virulent RB-1B strain from those caused by the vaccine CVI-988 strain in chicken embryonic fibroblasts. This has been hard to accomplish by standard molecular tests due to the close sequence similarities of the two viruses. To our knowledge, this study is the first ever to propose an RNA test based on the differential detection of splicing events as a potential assay.