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Marmota monax

ABSTRACT: Intrahepatic transcriptional signature associated with response to interferon-a treatment in the woodchuck model of chronic hepatitis B

PROVIDER: PRJNA291589 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2136860_1.fastq.gz	Fastqsanger.gz
	SRR2136860_2.fastq.gz	Fastqsanger.gz
	SRR2136870_1.fastq.gz	Fastqsanger.gz
	SRR2136870_2.fastq.gz	Fastqsanger.gz
	SRR2136880_1.fastq.gz	Fastqsanger.gz

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Project description:The Eastern woodchuck (Marmota monax) is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to the human hepatitis B virus (HBV). The woodchuck is used as an animal model for studying chronic hepatitis B (CHB) and HBV-associated hepatocellular carcinoma (HCC) in humans, but the lack of sequence information has hitherto precluded functional genomics analysis. To address this major limitation of the model, we report here the sequencing, assembly and annotation of the woodchuck transcriptome, together with the generation of custom woodchuck microarrays. Using this new platform, we characterized the transcriptional response to persistent WHV infection and WHV-induced HCC. This revealed that chronic WHV infection, like HBV, is associated with (i) a limited intrahepatic type I interferon response, (ii) intrahepatic induction of markers associated with T cell exhaustion, (iii) elevated levels of suppressor of cytokine signaling 3 (SOCS3) in the liver, and (iv) intrahepatic accumulation of neutrophils. Underscoring the translational value of the woodchuck model, this study also determined that WHV-induced HCC shares molecular characteristics with a subtype of human HCC with poor prognosis. Conclusion: Our data establish the translational value of the woodchuck model and provide new insights into immune pathways which may play a role either in the persistence of HBV infection or the sequelae of CHB. Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine non-tumor vs. tumor gene expression in liver samples obtained from animals chronically infected with WHV (n=13). Multiple technical replicates per woodchuck sample are included.

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