First full HCV infection model

Nature India ◽  
2012 ◽  
Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1407 ◽  
Author(s):  
Aydin ◽  
Kurt ◽  
Song ◽  
Lin ◽  
Osman ◽  
...  

Hepatitis C virus (HCV) infection compromises the natural defense mechanisms of the liver leading to a progressive end stage disease such as cirrhosis and hepatocellular carcinoma (HCC). The hepatic stress response generated due to viral replication in the endoplasmic reticulum (ER) undergoes a stepwise transition from adaptive to pro-survival signaling to improve host cell survival and liver disease progression. The minute details of hepatic pro-survival unfolded protein response (UPR) signaling that contribute to HCC development in cirrhosis are unknown. This study shows that the UPR sensor, the protein kinase RNA-like ER kinase (PERK), mediates the pro-survival signaling through nuclear factor erythroid 2-related factor 2 (NRF2)-mediated signal transducer and activator of transcription 3 (STAT3) activation in a persistent HCV infection model of Huh-7.5 liver cells. The NRF2-mediated STAT3 activation in persistently infected HCV cell culture model resulted in the decreased expression of hepatocyte nuclear factor 4 alpha (HNF4A), a major liver-specific transcription factor. The stress-induced inhibition of HNF4A expression resulted in a significant reduction of liver-specific microRNA-122 (miR-122) transcription. It was found that the reversal of hepatic adaptive pro-survival signaling and restoration of miR-122 level was more efficient by interferon (IFN)-based antiviral treatment than direct-acting antivirals (DAAs). To test whether miR-122 levels could be utilized as a biomarker of hepatic adaptive stress response in HCV infection, serum miR-122 level was measured among healthy controls, and chronic HCV patients with or without cirrhosis. Our data show that serum miR-122 expression level remained undetectable in most of the patients with cirrhosis (stage IV fibrosis), suggesting that the pro-survival UPR signaling increases the risk of HCC through STAT3-mediated suppression of miR-122. In conclusion, our data indicate that hepatic pro-survival UPR signaling suppresses the liver-specific HNF4A and its downstream target miR-122 in cirrhosis. These results provide an explanation as to why cirrhosis is a risk factor for the development of HCC in chronic HCV infection.


2000 ◽  
Vol 28 (03n04) ◽  
pp. 351-360 ◽  
Author(s):  
Jong-Chol Cyong ◽  
Sun-Min Kim ◽  
Koji Iijima ◽  
Takao Kobayashi ◽  
Minoru Furuya

Hepatitis C virus (HCV) infection frequently causes chronic hepatitis, which is linked to the development of liver cirrhosis and hepatocellular carcinoma. Most physicians who practice Kampo medicine in Japan have observed that Kampo medicine can be as effective as interferon therapy in the treatment of chronic hepatitis C. In the present study, to evaluate the effect of Kampo medicine on chronic hepatitis C, clinical treatment was assessed in short-term and long-term study, and it was shown that Ninjin-yoei-to (Formula ginseng compositae: TJ-108 was very effective. Therefore, to find the most active herbal component of TJ-108, in the treatment of HCV, Citrus Unshiu Peel, Schisandra Fruit, and Polygala Root, which are specific to TJ-108, were screened using an in vitro HCV infection model. Among the three herbs, Schisandra Fruit was found to be most active. In the next step, Gomisin A, an active component of Schisandra Fruit, was studied using an in vitro model with MOLT-4 cells and an animnal model of immunologically induced acute hepatic failures. It is concluded that the therapeutic effect of TJ-108 on chronic hepatitis C is from the inhibitory effect on HCV infection, and also from the protective effect on immunological hepatopathy of Schisandra Fruit and its lignan component, Gomisin A.


2012 ◽  
Vol 05 (06) ◽  
pp. 1250056 ◽  
Author(s):  
SHIFEI WANG ◽  
DINGYU ZOU

In this paper, we investigate global dynamics for a distributed time delayed HCV infection model. Our model admits two possible equilibria, an uninfected equilibrium and infected equilibrium depending on the basic reproduction number. By employing the method of Lyapunov functional, we prove that the uninfected equilibrium is global asymptotically stable if the basic reproduction number is less than one, it is unstable and the infected equilibrium is global asymptotically stable if the basic reproduction number is larger than one. The simulations results are in good accordance with our analytic results.


2021 ◽  
Vol 21 (8) ◽  
Author(s):  
Jinling Dong ◽  
Tiantian Wu ◽  
Ying Zhang ◽  
Zhihong Xie ◽  
Jie He

Background: There is a great need for further study on the mechanism of HCV infection or its pathopoiesis mechanism. Therefore, an HCV infection model was used to analyze the mechanisms of transcriptional and post-transcriptional regulation of gene expression. Methods: The detections of transcriptome and microRNAs expressions in Huh7.5.1 cells infected with JFH-1 were conducted with next-generation sequencing. Moreover, bioinformatics data were obtained. Results: There were 21,827,299, and 42,588,251 reads qualified Illumina read pairs obtained from JFH-1-infected (HCV) and non-infected (blank) Huh7.5.1 cells, respectively. Moreover, 678 and 1,041 mRNAs data with a length of 101 bp from HCV and blank Huh7.5.1 cells cDNA sequence were generated, respectively. The results of comparative transcriptome sequencing analysis declared 460 differentially expressed mRNAs in HCV-infected cells, including 152 upregulated mRNAs and 308 downregulated mRNAs (HCV vs. blank). Gene Ontology (GO) and KEGG pathway enrichment analyses indicated the involved pathways, such as MAPK, p53, and PI3K/Akt signaling pathways, as well as oocyte meiosis and pathways in cancer. Conclusions: Our work confirmed the transcriptome and microRNA data profiling from the cell model of HCV infection with JFH-1 using next-generation sequencing (NGS). Furthermore, the gene expression and regulation information or signaling pathways associated with the pathopoiesis mechanism of HCV infection were identified.


2001 ◽  
Vol 120 (5) ◽  
pp. A567-A567 ◽  
Author(s):  
E JAECKEL ◽  
M CORNBERG ◽  
T SANTANTONIO ◽  
J MAYER ◽  
H WEDEMEYER ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A366-A366
Author(s):  
C MAZZEO ◽  
F AZZAROLI ◽  
A COLECCHIA ◽  
S DISILVIO ◽  
A DORMI ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document