Abstract
BackgroundMarek’s disease virus (MDV) is an oncogenic herpesvirus that can cause T-cell lymphomas in chicken. Long noncoding RNA (lncRNA) is strongly associated with various cancers and many other diseases. In chickens, lncRNAs have not been comprehensively identified. Here, we profiled mRNA and lncRNA repertoires in three groups of spleens from MDV-infected and non-infected chickens, including seven tumorous spleens (TS) from MDV-infected chickens, five spleens from the survivors (SS) without lesions after MDV infection, and five spleens from noninfected chickens (NS), to explore the underlying mechanism of host resistance in Marek’s disease (MD).ResultsBy using a precise lncRNA identification pipeline, we identified 1315 putative lncRNAs and 1166 known lncRNAs in spleen tissue. Genomic features of putative lncRNAs were characterized. Differentially expressed (DE) mRNAs, putative lncRNAs, and known lncRNAs were profiled among three groups. We found that several specific intergroup differentially expressed genes were involved in important biological processes and pathways, including B cell activation and the Wnt signaling pathway; some of these genes were also found to be the hub genes in the co-expression network analyzed by WGCNA. Network analysis depicted both intergenic correlation and correlation between genes and MD traits. Five DE lncRNAs including MSTRG.360.1, MSTRG.6725.1, MSTRG.6754.1, MSTRG.15539.1, and MSTRG.7747.5 strongly correlated with MD-resistant candidate genes, such as IGF-I, CTLA4, HDAC9, SWAP70, CD72, JCHAIN, CXCL12, and CD8B, suggesting that lncRNAs may affect MD resistance and tumorigenesis in chicken spleens through their target genes.ConclusionsOur results provide both transcriptomic and epigenetic insights on MD resistance and its pathological mechanism. The comprehensive lncRNA and mRNA transcriptomes in MDV-infected chicken spleens were profiled. Co-expression analysis identified integrated lncRNA-mRNA and gene-gene interaction networks, implying that hub genes or lncRNAs exert critical influence on MD resistance and tumorigenesis.
Highlights
Marek’s disease virus (MDV) is an oncogenic herpesvirus that can cause T-cell lymphomas in chicken
Identification of Long noncoding RNA (lncRNA) A total of 17 samples were used for this study, including seven tumorous spleens (TS) and five spleens of survivors (SS) from MDV-infected chickens, and five noninfected spleens (NS) from mock infected chickens
We identified 1166 known lncRNAs through aligning with the lncRNAs either in NONCODE v5.0, an integrated non-coding RNA database, or in ALDB, a domestic-animal long noncoding RNA database (Additional file 1)
Summary
Marek’s disease virus (MDV) is an oncogenic herpesvirus that can cause T-cell lymphomas in chicken. Marek’s disease (MD) is a complex immunosuppressive disease It can cause paralysis, neuroinflammation, and chronic depletion, as well as lymphomas in chicken viscera and muscle tissue [17, 18]. MD is caused by Marek’s disease virus (MDV), a double-stranded DNA α-herpesvirus. The infectious life cycle of MDV in susceptible chicken lines can be divided into four stages: (1) establishment of primary infection; (2) semi-productive lytic viral replication in lymphocytes; (3) immune evasion and latency; and (4) tumor metastasis stage [21]. MDV has proven to be a valuable model virus for studying several human diseases caused by other herpesviruses; the MDV-chicken system gives us a highly available and efficacious model to understand virus-induced lymphomagenesis. As tumor formation occurs only a few weeks after infection with different MDV strains in chicken lines, it is possible to perform herpesvirus-induced oncogenesis studies in chickens [22]
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