Long intergenic non-coding RNA GALMD3 in chicken Marek’s disease

Abstract

Long intergenic non-coding RNAs (lincRNAs) are transcribed from non-coding DNA sequences. Studies have revealed that aberrant expressions of lincRNAs are associated with various types of cancers and neurological disorders. Marek’s disease (MD) is a highly contagious T-cell lymphoid neoplasia of chicken induced by Marek’s disease virus (MDV). In this study, we first identified and validated linc-GALMD3 highly expressed in MDV-infected CD4+ T cells by RNA-Seq and qRT-PCR. By RNA-Seq analysis in MDCC-MSB1 cells after loss of function of linc-GALMD3 by shRNA, we found that linc-GALMD3 could positively cis-regulate its downstream gga-miR-223 gene expression. In contrast, it could trans-regulate the 748 differentially expressed genes (FDR < 0.01) that were mainly enriched into mitochondrial structure and cell cycle processes using GO analysis. Of these, the most significantly expressed gene EPYC might cause iris lesion in MD. The other eight genes, NDUFA4, NDUFB6, NDUFV1, NDUFS8, SDHB, UQCRC1, UQCRC2, and COX7A2, actively participated in oxidative phosphorylation in mitochondrial dysfunction and cell death. Most importantly, we found that the MDV replication was repressed when linc-GALMD3 was knocked down in CEF cells. Our results suggested that linc-GALMD3 might be a critical regulator in chicken MD and could be used as a candidate-promising mark for MD prevention, diagnosis, and treatment.

Mapping QTL Associated with Resistance to Avian Oncogenic Marek’s Disease Virus (MDV) Reveals Major Candidate Genes and Variants

“…These studies are usually done, not with relevant commercial lines, but with experimental or inbred lines and examine whole tissues, although recent work has investigated the host response to MDV in specific cells such as macrophages, which are an early target for the virus [ 21 , 22 ]. Recent studies on the role of long non-coding RNAs [ 23 , 24 ] and microRNAs (in both the host and virus) have also been carried out [ 25 , 26 , 27 ], including a study of serum exosomes from lymphoma-bearing birds [ 28 ]. In addition, the role of epigenetics in resistance to MDV has been studied, with regions of differential methylation between susceptible and resistant lines of birds highlighted [ 29 , 30 ].…”

Marek’s Disease Virus Infection Induced Mitochondria Changes in Chickens

“…Additionally, the AIFM2 gene, a gene with pro-apoptotic function and often being down-regulated in various cancers [42] was indeed significantly decreased in spleen of the line 7 2 infected birds. Moreover, two mPTP genes VDAC1 and VDAC2 , which was reported to be activated by linc-GALMD3 , an up-regulated long intergenic non-coding RNA in MDV infection leading to apoptosis and cell death [26], were also found significantly up-regulated in spleen samples of the line 7 2 infected birds. It has been reported that several viruses can induce apoptosis of lymphoid through multiple pathways.…”

“…One of the inbred lines, the line 6 3 , was selected for resistance to tumors, while the other, the line 7 2 , was selected for susceptibility, which provides valuable and unique models for immunity and tumorigenesis researches. Recently, a long intergenic non-coding RNA, GALMD3 , was identified being highly expressed post MDV-infection, which might cause mitochondrial dysfunction and lead to MD in chickens [26]. Although a great amount of efforts has been made for deciphering the virus infection and the host response, the link between MDV infection and mitochondria dynamics remains unclear.…”

Epigenetic Regulation by Non-Coding RNAs in the Avian Immune System

“…The loss of function of linc-GALMD3 will suppress miR-223 expression and MDV replication. Additionally, DEG analysis of RNA-Seq between the linc-GALMD3 knockdown and control MSB1 (MDCC-MSB1) cells showed that about 27 DEGs were also miR-223 target genes, which implied the cis regulatory mechanism of linc-GALMD3 on miR-223 [74]. The linc-GALMD3-miR-223-target DEGs interaction network could be used for further investigation during MDV infection.…”

“…LncRNAs act as an upstream regulator to modulate miRNA expression, thus exhibiting specific function during MD viral infection was also an approach for lncRNA to regulate MDV infection. linc-GALMD3, which has a higher expression level in CD4 + T cells after MDV infection, was found to be located on the upstream of the gene transcribes miR-223 [74]. The loss of function of linc-GALMD3 will suppress miR-223 expression and MDV replication.…”