868 LIVER X RECEPTOR a-MEDIATED LIPOGENESIS INDUCED BY HEPATITIS C VIRUS NS5A AND CORE PROTEINS REGULATES VIRAL REPLICATION IN AN IN VITRO MODEL

2012 ◽  
Vol 56 ◽  
pp. S338
Author(s):  
S. Pisonero-Vaquero ◽  
M.V. García-Mediavilla ◽  
F. Jorquera ◽  
P.L. Majano ◽  
J. Gonzalez-Gallego ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Replication ◽  
In Vitro Model ◽  
Liver X Receptor ◽  
Core Proteins ◽  
Vitro Model

scholarly journals Future Directions in the Treatment of Patients with Chronic Hepatitis C Virus Infection

1999 ◽  
Vol 13 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Robert G Gish
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
High Throughput Screening ◽  
In Vitro Model ◽  
Single Agent ◽  
Protein Translation ◽  
In Vitro Translation ◽  
Biotechnology Companies ◽  
Vitro Model

Hepatitis C virus (HCV) infects over 170 million people worldwide. While interferon is currently the most used single agent therapy, this drug may result in a sustained loss of virus from the blood in only up to 15% of patients; new options for treatment are needed. With the release of ribavirin in North America and Europe, a viral clearance rate or ‘cure’ may be attained in up to 40% of patients. Developing successful antiviral therapy that prevents or delays the development of cirrhosis, liver failure and liver cancer as well as decreasing the demand for liver transplantation are clearly identified goals. Unfortunately, there is no complete in vitro model of HCV replication or translation. Due to the lack of an animal or cell culture model of HCV infection, in vitro translation screening systems to identify inhibitors of HCV protein translation are being evaluated by a large number of biotechnology companies. With advancing computer technology, high throughput screening processes are now possible and can be joined to specific in vitro model testing systems. Along with examining some of the information known about HCV therapy and the HCV genome, the present review discusses potential targets for new therapies and identifies therapeutic agents that are nearing clinical application

804 EFFECT OF HCV NS5A AND CORE PROTEINS AND VIRAL REPLICATION ON LXRa-MEDIATED LIPOGENIC GENES INDUCTION IN AN IN VITRO MODEL

2011 ◽  
Vol 54 ◽  
pp. S323
Author(s):  
E. Lima-Cabello ◽  
M.V. García-Mediavilla ◽  
S. Pisonero-Vaquero ◽  
F. Jorquera ◽  
P.L. Majano ◽  
...  
Keyword(s):  
Viral Replication ◽  
In Vitro Model ◽  
Lipogenic Genes ◽  
Core Proteins ◽  
Vitro Model

scholarly journals An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation

2005 ◽  
Vol 42 (5) ◽  
pp. 744-751 ◽  
Author(s):  
Karim Abid ◽  
Valerio Pazienza ◽  
Andrea de Gottardi ◽  
Laura Rubbia-Brandt ◽  
Beatrice Conne ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Vitro Model ◽  
Virus Genotype ◽  
Vitro Model ◽  
Genotype 3A

scholarly journals In-vitro model systems to study Hepatitis C Virus

2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Usman Ali Ashfaq ◽  
Shaheen N Khan ◽  
Zafar Nawaz ◽  
Sheikh Riazuddin
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
In Vitro Model ◽  
Model Systems ◽  
Vitro Model

Human Cytomegalovirus Infection of Primitive Hematopoietic Progenitor Cells: A Model for Latency.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1703-1703
Author(s):  
Felicia D. Goodrum ◽  
Craig T. Jordan ◽  
Scott S. Terhune ◽  
Kevin P. High ◽  
Thomas Shenk
Keyword(s):  
Bone Marrow ◽  
Viral Replication ◽  
Progenitor Cells ◽  
Human Cytomegalovirus ◽  
In Vitro Model ◽  
Latent Infection ◽  
Cmv Infection ◽  
Aids Patients ◽  
Vitro Model

Abstract Human cytomegalovirus (CMV) is beta-herpesvirus that infects the majority of the population worldwide and establishes a lifelong relationship with its host by way of a latent infection. Although, CMV is of little consequence to healthy individuals, reactivation of CMV from latency can cause life-threatening disease in immunocompromised individuals such as bone marrow transplant recipients and AIDS patients. CMV establishes a latent infection in cells of the hematopoietic system. The focus of our work is to elucidate the mechanisms governing a latent infection and reactivation from latency. It is likely that both viral and cellular mechanisms govern the latent program. We have developed a novel in vitro model for CMV latency using primary human hematopoietic progenitors. Using this model to compare CMV infection in CD34+ hematopoietic subpopulations, the outcome of CMV infection was found to depend on the nature of the subpopulation of cells infected. Only primitive CD34+/CD38− progenitor cells harboured an infection with the hallmarks of latency. This subpopulation transiently expressed a unique subset of CMV genes in the absence of viral replication. Importantly, viral replication could be reactivated from this subpopulation. Other primitive (CD34+/c-kit+) and more mature (CD34+/CD38+ and CD34+/c-kit−) subpopulations resulted in an apparently abortive infection. Strikingly, a CD34+ subpopulation expressing a stem cell phenotype supported a productive infection. These results indicate that cellular determinants contribute to the outcome of HCMV infection in hematopoietic cells. Further, we have also demonstrated that viral determinants play a role in establishing a latent infection using our in vitro model. Comparing the clinical Toledo and FIX strains and the laboratory-adapted AD169 strain of CMV, only the clinical strains were able to establish an infection consistent with latency. AD169, by contrast, replicated productively. Genetic sequences unique to clinical strains have been identified and may contribute to its ability to establish a latent infection in vitro. These studies indicate that both viral and cellular determinants contribute to the establishment of CMV latency. Furthermore, these determinants may serve as targets for CMV disease prophylaxis following bone marrow transplantation or in AIDS patients.

scholarly journals Hepatitis C Virus Core Protein Is a Dimeric Alpha-Helical Protein Exhibiting Membrane Protein Features

2005 ◽  
Vol 79 (17) ◽  
pp. 11353-11365 ◽  
Author(s):  
Steeve Boulant ◽  
Christophe Vanbelle ◽  
Christine Ebel ◽  
François Penin ◽  
Jean-Pierre Lavergne
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Rna Binding ◽  
Core Protein ◽  
Limited Proteolysis ◽  
Hydrophobic Domain ◽  
Fluorescence Measurements ◽  
Hcv Core Protein ◽  
Core Proteins

ABSTRACT The building block of hepatitis C virus (HCV) nucleocapsid, the core protein, together with viral RNA, is composed of different domains involved in RNA binding and homo-oligomerization. The HCV core protein 1-169 (CHCV169) and its N-terminal region from positions 1 to 117 (CHCV117) were expressed in Escherichia coli and purified to homogeneity suitable for biochemical and biophysical characterizations. The overall conformation and the oligomeric properties of the resulting proteins CHCV169 and CHCV117 were investigated by using analytical centrifugation, circular dichroism, intrinsic fluorescence measurements, and limited proteolysis. Altogether, our results show that core protein (CHCV169) behaves as a membranous protein and forms heterogeneous soluble micelle-like aggregates of high molecular weight in the absence of detergent. In contrast, it behaves, in the presence of mild detergent, as a soluble, well-folded, noncovalent dimer. Similar to findings observed for core proteins of HCV-related flaviviruses, the HCV core protein is essentially composed of α-helices (50%). In contrast, CHCV117 is soluble and monodispersed in the absence of detergent but is unfolded. It appears that the folding of the highly basic domain from positions 2 to 117 (2-117 domain) depends on the presence of the 117-169 hydrophobic domain, which contains the structural determinants ensuring the binding of core with cellular membranes. Finally, our findings provide valuable information for further investigations on isolated core protein, as well as for attempts to reconstitute nucleocapsid particles in vitro.

scholarly journals The FUSE Binding Protein Is a Cellular Factor Required for Efficient Replication of Hepatitis C Virus

2008 ◽  
Vol 82 (12) ◽  
pp. 5761-5773 ◽  
Author(s):  
Zhengbin Zhang ◽  
Dylan Harris ◽  
Virendra N. Pandey
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Viral Replication ◽  
Molecular Mechanisms ◽  
Nonstructural Protein ◽  
Binding Protein ◽  
Cellular Factor ◽  
Nontranslated Region ◽  
Efficient Replication

ABSTRACT Hepatitis C virus (HCV) infection is the leading cause of liver cirrhosis and hepatocellular carcinoma and one of the primary indications for liver transplantation. The molecular mechanisms underlying the actions of host factors in HCV replication remain poorly defined. FUSE (far upstream element of the c-myc proto-oncogene) binding protein (FBP) is a cellular factor that we have identified as a binder of HCV 3′ nontranslated region (3′NTR). Mapping of the binding site showed that FBP specifically interacts with the poly(U) tract within the poly(U/UC) region of the 3′NTR. Silencing of FBP expression by small interfering RNA in cells carrying HCV subgenomic replicons severely reduced viral replication, while overexpression of FBP significantly enhanced viral replication. We confirmed these observations by an in vitro HCV replication assay in the cell-free replicative lysate, which suggested that there is a direct correlation between the cellular FBP level and HCV replication. FBP immunoprecipitation coprecipitated HCV nonstructural protein 5A (NS5A), indicating that FBP interacts with HCV NS5A, which is known to function as a link between HCV translation and replication. Although FBP is mainly localized in the nucleus, we found that in MH14 cells a significant level of this protein is colocalized with NS5A in the cytosol, a site of HCV replication. While the mechanism of FBP involvement in HCV replication is yet to be delineated, our findings suggest that it may be an important regulatory component that is essential for efficient replication of HCV.

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