Transcriptional profiling of Hepatitis C virus HCV core transgenic mice liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: ML Chang
PROVIDER: E-GEOD-16403 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Transcriptional profiling of HCV core transgenic mice liver comparing nontransgenic mice liver or HCV core transgenic mice liver with various core expression levels.
2013-12-31 | GSE16403 | GEO
Project description:Transcriptional profiling of Hepatitis C virus HCV core transgenic mice liver
| PRJNA116297 | ENA
Project description:We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Goal and objectives: To study the requirement of HCV viral proteins and/or environmental factors (such as alcohol or obesity) in synergistic liver caner development in HCV Core or NS5A Tg mice given alcohol or high-cholesterol high-fat diet, mice were fed alcohol or high-cholesterol high-fat diet and liver tissues from these mice were examined for gene profiles. Alcohol or obesity contributes to synergistic tumor incidence and HCV Core or Ns5a-induced effects. Thus, analysis of gene profiling of these transgenic mice will identify the critical pathways to induce synergistic tumor formation caused by alcohol or obesity.
2014-09-16 | GSE61435 | GEO
Project description:Hepatitis C Virus (HCV) core protein plays a major role in HCV mediated liver pathologies. We have previously reported that HCV core variants isolated from tumoral (T) and non-tumoral (NT) livers were capable to alleviate Smad transcriptional activity and to shift TGF-β responses from tumor suppressor effects to tumor promotion. To comprehensively appreciate the consequences of core-mediated deregulation of Smad signaling on TGF-b target gene expression, Affimetrix microarrays were performed. Microarray analyses demonstrate that HCV core expression in hepatocytes modulates TGF-b target gene expression. Furthermore, most of the genes modulated in core expressing hepatocytes after TGF-b treatment were already regulated in these non treated cells suggesting that HCV core is capable to activate latent TGF-b. Transcriptome analysis was performed on primary hepatocytes from transgenic mice expressing either Core T or core NT or their control littermates treated or not with TGF-b.
2012-03-03 | E-GEOD-36220 | biostudies-arrayexpress
Project description:Viral hepatitis and aflatoxin B1 (AFB1) exposure are common risk factors for hepatocellular carcinoma (HCC). The incidence of HCC in individuals co-exposed to hepatitis C (HCV) or B virus and AFB1 is greater than could be explained by the additive effect, yet the mechanisms are poorly understood due to lack of an animal model. This study investigated the outcomes and mechanisms of combined exposure to HCV and AFB1. We hypothesized that HCV transgenic (HCV-Tg; expressing core, E1, E2, and p7, nucleotides 342-2771) mice will be prone to hepatocarcinogenesis when exposed to AFB1. Neonatal (7 days old) HCV-Tg or C57BL/6J wild-type mice were exposed to AFB1 (6 ug/g bw) or tricaprylin vehicle (15 ul/g bw) and male offspring were followed for up to 12 months. No liver lesions were observed in vehicle-treated wild type or HCV-Tg mice. Tumors (adenomas or carcinomas) and preneoplastic lesions (hyperplasia or foci) were observed in 22.5% (9 of 40) of AFB1-treated wild-type mice. In HCV-Tg, the incidence of tumorous or pre-tumorous lesions was significantly elevated (50%, 18 of 36), with the difference largely due to a 2.5-fold increase in the incidence of adenomas (30.5% vs 12.5%). While oxidative stress and steato-hepatisis were observed in both AFB1-treated groups, molecular changes indicative of the enhanced inflammatory response and altered lipid metabolism were more pronounced in HCV-Tg mice. In summary, HCV proteins core, E1, E2 and p7 are sufficient to reproduce the additive co-carcinogenic effect of HCV and AFB1 which is a known clinical phenomenon. HCV transgenic mice (SL-139 strain, pAlbSVPA-HCV-S, containing the structural genes core, E1, E2, and p7, nucleotides 342-2771 of HCV genotype 1b, strain N, under the control of the murine albumin promoter/enhancer) on C57BL/6J (Jackson Laboratory, Bar Harbor, ME) background were previously reported in Lerat et al (Lerat et al., Gastroenterology 122, 352-365, 2002). Transgenic animals were identified after weaning as detailed in Korenaga et al (Korenaga et al., J Biol. Chem. 280, 37481-37488, 2005). Neonatal (7 days old) mice were administered a single dose of AFB1 (6 ug/g bw) or tricaprylin vehicle (15 ul/g bw) by intra-peritoneal injection. Male mice were maintained on the regular animal chow with free access to food and water for up to 12 months. All animal experiments were approved by the UNC Animal Care and Use Committee. There were 20 liver samples used for microarray analysis (12 month time point). All samples were run in one batch. There are 4 groups: WT/Control (4 samples - all biological replicates, i.e., different animals); WT/AFB1 (6 samples); HCV/Control (4 samples); HCV/AFB1 (6 samples). This was a 2 color design with a common reference mRNA. No dye swaps or replicate arrays were included.
2011-01-25 | E-GEOD-26838 | biostudies-arrayexpress
Project description:We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Goal and objectives: To study the requirement of HCV viral proteins and/or environmental factors (such as alcohol or obesity) in synergistic liver caner development in HCV Core or NS5A Tg mice given alcohol or high-cholesterol high-fat diet, mice were fed alcohol or high-cholesterol high-fat diet and liver tissues from these mice were examined for gene profiles. Alcohol or obesity contributes to synergistic tumor incidence and HCV Core or Ns5a-induced effects. Thus, analysis of gene profiling of these transgenic mice will identify the critical pathways to induce synergistic tumor formation caused by alcohol or obesity. Liver samples for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain gene profiling data in order to increase understanding the pathways. To perform gene array and proteomic analyses, mice were fed alcohol or high-cholesterol high-fat for 12 months and euthanized after 12 months feeding. Livers were collected at the time of euthanasia.
2014-09-16 | E-GEOD-61435 | biostudies-arrayexpress
Project description:Although treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) results in high rates of cure, liver fibrosis does not resolve immediately after HCV eradication. Resolution of fibrosis occurs in some, but not all patients, after HCV cure, and hepatic decompensation and hepatocellular carcinoma can still occur in patients with pre-existing cirrhosis. We hypothesized that evaluation of the host liver proteome in the context of HCV treatment would provide insight into how inflammatory and fibrinogenic pathways change upon HCV eradication. We evaluated the whole liver proteome and phosphoproteome using paired liver biopsies from 8 HCV-infected patients collected before or immediately after treatment with DAAs in clinical trials. We identify interferon stimulated proteins as the predominant pathways that decrease with HCV treatment, which is consistent with previous analyses of the liver transcriptome during DAA therapy. While there was no change in the proteome of pathways associated with liver fibrosis, we identified a decrease in the phosphoproteome signature for ERK1/ERK2 as a result of HCV treatment. Conclusion: There is a reduction in the endogenous interferon-mediated antiviral response and alterations in the phosphoproteome that may precede resolution of fibrosis in the liver immediately after treatment of HCV with DAAs.
2023-03-11 | PXD024846 | Pride
Project description:Viral hepatitis and aflatoxin B1 (AFB1) exposure are common risk factors for hepatocellular carcinoma (HCC). The incidence of HCC in individuals co-exposed to hepatitis C (HCV) or B virus and AFB1 is greater than could be explained by the additive effect, yet the mechanisms are poorly understood due to lack of an animal model. This study investigated the outcomes and mechanisms of combined exposure to HCV and AFB1. We hypothesized that HCV transgenic (HCV-Tg; expressing core, E1, E2, and p7, nucleotides 342-2771) mice will be prone to hepatocarcinogenesis when exposed to AFB1. Neonatal (7 days old) HCV-Tg or C57BL/6J wild-type mice were exposed to AFB1 (6 ug/g bw) or tricaprylin vehicle (15 ul/g bw) and male offspring were followed for up to 12 months. No liver lesions were observed in vehicle-treated wild type or HCV-Tg mice. Tumors (adenomas or carcinomas) and preneoplastic lesions (hyperplasia or foci) were observed in 22.5% (9 of 40) of AFB1-treated wild-type mice. In HCV-Tg, the incidence of tumorous or pre-tumorous lesions was significantly elevated (50%, 18 of 36), with the difference largely due to a 2.5-fold increase in the incidence of adenomas (30.5% vs 12.5%). While oxidative stress and steato-hepatisis were observed in both AFB1-treated groups, molecular changes indicative of the enhanced inflammatory response and altered lipid metabolism were more pronounced in HCV-Tg mice. In summary, HCV proteins core, E1, E2 and p7 are sufficient to reproduce the additive co-carcinogenic effect of HCV and AFB1 which is a known clinical phenomenon. HCV transgenic mice (SL-139 strain, pAlbSVPA-HCV-S, containing the structural genes core, E1, E2, and p7, nucleotides 342-2771 of HCV genotype 1b, strain N, under the control of the murine albumin promoter/enhancer) on C57BL/6J (Jackson Laboratory, Bar Harbor, ME) background were previously reported in Lerat et al (Lerat et al., Gastroenterology 122, 352-365, 2002). Transgenic animals were identified after weaning as detailed in Korenaga et al (Korenaga et al., J Biol. Chem. 280, 37481-37488, 2005). Neonatal (7 days old) mice were administered a single dose of AFB1 (6 ug/g bw) or tricaprylin vehicle (15 ul/g bw) by intra-peritoneal injection. Male mice were maintained on the regular animal chow with free access to food and water for up to 12 months. All animal experiments were approved by the UNC Animal Care and Use Committee.
2011-01-25 | GSE26838 | GEO
Project description:Transcriptome study of hepatocytes isolated from transgenic mice expressing HCV core.
| PRJNA153123 | ENA
Project description:The hepatitis C virus (HCV) is one of the major risk factors for the development of hepatocellular carcinoma (HCC). Nevertheless, transgenic mice which express the whole HCV polyprotein (HCV-Tg) do not develop HCC. Whereas chronic HCV infection causes inflammation in patients, in HCV-Tg mice, the host immune reaction against viral proteins is lacking. We aimed to test the role of HCV proteins in HCC development on the background of chronic inflammation in vivo. We crossed the HCV-Tg mice which do not produce HCC with the Mdr2-knockout (Mdr2-KO) mice which develop inflammation-associated HCC, to generate Mdr2-KO/HCV-Tg mice. We studied the effect of the HCV transgene on tumor incidence, hepatocyte mitosis and apoptosis, and on gene expression in the liver of produced mice.
2009-03-22 | GSE12184 | GEO