Exploration of Alternative Splicing (AS) Events in MDV-Infected Chicken Spleens.

Lulu Wang,Changjun Liu,Ling Lian,Yiming Yuan,Gang Zheng,Hao Zhang,Ziyi Wang

doi:10.3390/genes12121857

Abstract

Marek’s disease (MD) was an immunosuppression disease induced by Marek’s disease virus (MDV). MD caused huge economic loss to the global poultry industry, but it also provided an ideal model for studying diseases induced by the oncogenic virus. Alternative splicing (AS) simultaneously produced different isoform transcripts, which are involved in various diseases and individual development. To investigate AS events in MD, RNA-Seq was performed in tumorous spleens (TS), spleens from the survivors (SS) without any lesion after MDV infection, and non-infected chicken spleens (NS). In this study, 32,703 and 25,217 AS events were identified in TS and SS groups with NS group as the control group, and 1198, 1204, and 348 differently expressed (DE) AS events (p-value < 0.05 and FDR < 0.05) were identified in TS vs. NS, TS vs. SS, SS vs. NS, respectively. Additionally, Function enrichment analysis showed that ubiquitin-mediated proteolysis, p53 signaling pathway, and phosphatidylinositol signaling system were significantly enriched (p-value < 0.05). Small structural variations including SNP and indel were analyzed based on RNA-Seq data, and it showed that the TS group possessed more variants on the splice site region than those in SS and NS groups, which might cause more AS events in the TS group. Combined with previous circRNA data, we found that 287 genes could produce both circular and linear RNAs, which suggested these genes were more active in MD lymphoma transformation. This study has expanded the understanding of the MDV infection process and provided new insights for further analysis of resistance/susceptibility mechanisms.

Highlights

Marek’s disease (MD), induced by Marek’s disease virus (MDV), caused huge economic losses to the global poultry industry [1]
MDV showed some similar features with human herpesvirus 6 (HHV-6) [5] and Epstein Barr virus (EBV) [6], such as they all can integrate into the host genome [7,8,9] and were related to lymphoproliferative cancers [10,11]
Hthoewreevweerr,einmclourseioinncjulunscitoionnjurenacdtisonwecroeulnetsss thhaann sskkiippppiinnggjujunncctitoionncoreuandts of SNLRAP, 2SV(TIaLb. lHe o1w),ewvehri,cihncwluassiocnonjusnisctteinotnwreiathdsthweearegalersossethgaenl sekleipctprionpghjournecstiisornesreualtd. s of NRP2 (Table 1), which was consistent with the agarose gel electrophoresis result

Summary

Introduction

Marek’s disease (MD), induced by Marek’s disease virus (MDV), caused huge economic losses to the global poultry industry [1]. Vaccines can just prevent neuropathy, oncogenic disease, and immunosuppression. They could not prevent MDV transmission or infection [3]. MDV was similar to human herpesvirus 1 (HSV-1) and human herpesvirus 3 (VZV) from the genetic point of view [9]. Many studies focused on elaborating the mechanism of MDV infection from the perspective of genetics to provide a basis for the development of vaccines and disease treatment induced by the oncogenic virus

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Results

Conclusion