NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE36533 Query DataSets for GSE36533
Status Public on Apr 11, 2012
Title Transcriptomic analysis of the woodchuck model of chronic hepatitis B: Liver gene expression in uninfected, resolved and chronically infected woodchucks
Organism Marmota monax
Experiment type Expression profiling by array
Summary 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.
 
Overall design Custom microarrays, generated from sequences obtained in transcriptome sequencing of woodchuck liver and PBMCs, were used to examine liver gene expression in animals chronically infected with WHV (n=13), animals that had resolved WHV infection at least 12 months prior (R; n=11; range 12-18 months), and uninfected animals (U; n=10). Multiple technical replicates per woodchuck sample are included.
 
Contributor(s) Fletcher SP, Chin DJ, Ji Y, Iniguez AL, Taillon B, Swinney DC, Ravindran P, Cheng DT, Bitter H, Lopatin U, Ma H, Klumpp K, Menne S
Citation(s) 22431061
Submission date Mar 15, 2012
Last update date Jan 18, 2013
Contact name Donavan Cheng
E-mail(s) donavan.cheng@gmail.com
Organization name Hoffmann-LaRoche
Department Translational Research Sciences
Street address 340 Kingsland Ave
City Nutley
State/province NJ
ZIP/Postal code 07110
Country USA
 
Platforms (1)
GPL15354 NimbleGen Woodchuck Gene Expression HX3 Microarray
Samples (123)
GSM896274 M3353-liver-Uninfected, 460771_A02
GSM896275 M3134-liver-Chronic, 460771_A03
GSM896276 M5376-liver-Chronic, 460781_A02
This SubSeries is part of SuperSeries:
GSE36250 Transcriptomic analysis of the woodchuck model of chronic hepatitis B
Relations
BioProject PRJNA155579

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE36533_RAW.tar 1.4 Gb (http)(custom) TAR (of PAIR)
Processed data included within Sample table
| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap