Marek’s Disease Virus Virulence Genes Encode Circular RNAs

Chasseur, Alexis Serge; Trozzi, Gabrielle; Istasse, Céline; Petit, Astrid; Rasschaert, Perrine; Denesvre, Caroline; Kaufer, Benedikt B.; Bertzbach, Luca D.; Muylkens, Benoît; Coupeau, Damien

doi:10.1128/jvi.00321-22

Cited by 18 publications

(23 citation statements)

References 84 publications

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“…The repeat long region of MDV has a complex arrangement of genes and expression patterns, including miRNAs [50, 51], internal ribosomal entry sites (IRES) [52], and circRNAs [53]. Of importance in the context of this report is the examination of mRNA splicing in the region spanning the 14 kDa family of nuclear proteins (Fig 2A, S2 Fig), whose transcripts are amongst the most highly expressed in epithelial skin cells (S3 Table).…”

Section: Resultsmentioning

confidence: 99%

Viral proteogenomic and expression profiling during fully productive replication of a skin-tropic herpesvirus in the natural host

Volkening¹,

Spatz

Ponnuraj

et al. 2023

Preprint

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Efficient transmission of herpesviruses is essential for dissemination in host populations; however, little is known about the viral genes that mediate transmission, mostly due to their close relationship to their natural host. Marek’s disease is a devastating herpesviral disease of chickens caused by Marek’s disease virus (MDV) and an excellent natural model to study skintropic herpesviruses and transmission. Similar to varicella zoster virus that causes chicken pox in humans, the only site where fully productive replication occurs is in epithelial skin cells and this is required for host to host transmission. Here, we enriched for actively replicating virus in feather follicle epithelial skin cells of live chickens to measure both viral transcription and protein expression using combined RNA sequencing and LC/MS-MS bottom-up proteomics. Enrichment produced a previously unseen breadth and depth of viral peptide sequencing. We confirmed protein translation for 84 viral genes at high confidence (1% FDR) and correlated relative protein abundance with RNA expression levels. Using a proteogenomic approach, we confirmed translation of most well-characterized spliced viral transcripts and identified a novel, abundant isoform of the 14 kDa transcript family via both intron-spanning sequencing reads as well as a high-quality junction-spanning peptide identification. We identified peptides representing alternative start codon usage in several genes and putative novel microORFs at the 5’ ends of two core herpesviral genes, pUL47 and ICP4, along with evidence of transcription and translation of the capsid scaffold protein pUL26.5. Using a natural animal host model system to examine viral gene expression provides a robust, efficient, and meaningful way of validating results gathered from cell culture systems.

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Section: Resultsmentioning

confidence: 99%

Viral proteogenomic and expression profiling during fully productive replication of a skin-tropic herpesvirus in the natural host

Volkening¹,

Spatz

Ponnuraj

et al. 2023

Preprint

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“…For instance, RLORF4 could regulate NF-κB pathway activation ( 18 , 19 ), and RLORF7 could interact with other cellular proteins, including HDAC1/2 and the multifunctional protein and “guardian of the genome” p53, and induce host cell apoptosis ( 20 , 42 ). In addition, transcriptional unit of the major viral oncogene encoding the Meq protein and the latency-associated transcripts (LATs) also regulate viral virulence ( 43 ). Our study proves that LORF3 does contribute to the pathogenesis and pathogenicity of DPV, but we still do not know how LORF3 functions.…”

Section: Discussionmentioning

confidence: 99%

“…The procedure was carried out as previously described ( 43 , 47 ). Nucleic acid synthesis inhibitor GCV and protein synthesis inhibitor CHX were used to determine the LORF3 gene type.…”

Section: Methodsmentioning

confidence: 99%

Characterization of a Unique Novel LORF3 Protein of Duck Plague Virus and Its Potential Pathogenesis

Shen

Ruan

Cheng

et al. 2023

J Virol

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“…A large variety of MDV circRNAs was identified through RNAsequencing, and the hot spots of circRNAs expression occurred on the major viral oncogenes in herpesviruses. Moreover, many noncanonical junction sites were observed in viral circRNAs compatible with the U2-dependent splicing machinery (39).…”

Section: Marek's Disease Virus (Mdv) Encoded Circrnasmentioning

confidence: 99%

Viral Circular RNAs and Their Possible Roles in Virus-Host Interaction

et al. 2022

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Circular RNAs (circRNAs) as novel regulatory molecules have been recognized in diverse species, including viruses. The virus-derived circRNAs play various roles in the host biological process and the life cycle of the viruses. This review summarized the circRNAs from the DNA and RNA viruses and discussed the biogenesis of viral and host circRNAs, the potential roles of viral circRNAs, and their future perspective. This review will elaborate on new insights gained on viruses encoded circRNAs during virus infection.

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Marek’s Disease Virus Virulence Genes Encode Circular RNAs

Cited by 18 publications

References 84 publications

Viral proteogenomic and expression profiling during fully productive replication of a skin-tropic herpesvirus in the natural host

Viral proteogenomic and expression profiling during fully productive replication of a skin-tropic herpesvirus in the natural host

Characterization of a Unique Novel LORF3 Protein of Duck Plague Virus and Its Potential Pathogenesis

Viral Circular RNAs and Their Possible Roles in Virus-Host Interaction

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