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Marek's Disease Virus Virulence Genes Encode Circular RNAs.
Alexis S Chasseur1, Gabrielle Trozzi1, Céline Istasse1
1Namur Research Institute for Life Sciences (NARILIS), Integrated Veterinary Research Unit (URVI), University of Namur, Namur, Belgium.
Journal of Virology
|April 12, 2022
Summary
This study reveals Marek's disease virus (MDV) produces circular RNAs (circRNAs) during infection. These viral circRNAs are linked to key MDV virulence genes, offering new insights into herpesvirus-induced cancers.
Area of Science:
- Virology and molecular biology, focusing on noncoding RNA in viral pathogenesis.
- Oncology, specifically virus-induced cancers and tumorigenesis.
Background:
- Circular RNAs (circRNAs) are functional noncoding RNAs implicated in gene regulation and cancer.
- Viral circRNAs are known in human herpesviruses linked to lymphoma.
- Marek's disease virus (MDV) is a model for herpesvirus-induced lymphoma, but its circRNAs were uncharacterized.
Purpose of the Study:
- To investigate viral circRNA expression in Marek's disease virus (MDV) infections.
- To characterize the full-length sequences and expression patterns of MDV-encoded circRNAs.
- To explore the role of these circRNAs in MDV pathogenesis and provide a tool for herpesvirus research.
Main Methods:
- Inverse PCR was used to identify and characterize circRNA expression during MDV replication, latency, and reactivation.
- Full-length sequencing and precise mapping of viral circRNAs were performed.
- Genome-wide bioinformatic analyses extracted back-splice junctions from lymphoma samples to identify circRNAs in vivo.
Main Results:
- A diverse range of viral circRNAs were identified from MDV repeat regions.
- Hot spots for circRNA expression included the Meq oncogene and latency-associated transcripts (LATs).
- Abundant circRNA expression was detected in vivo from key MDV virulence genes, with numerous noncanonical junctions observed.
Conclusions:
- This study provides the first evidence of viral circRNAs expressed during key stages of the MDV lifecycle.
- MDV circRNAs originate from critical virulence genes, contributing to the complexity of this pathogen.
- A bioinformatics pipeline was developed, enabling the identification of circRNAs in other herpesviruses.
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