Browsing by Subject "Hepatitis C virus"

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Open Access
Anti-cancer and anti-hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles
(Taylor and Francis Ltd, 2015) Çikla-Süzgün P.; Kaushik-Basu, N.; Basu, A.; Arora P.; Talele, T.T.; Durmaz I.; Çetin-Atalay, R.; Küçükgüzel, S.G.
Arachidonic acid is an unsaturated fatty acid liberated from phospholipids of cell membranes. NSAIDs are known as targets of cyclooxygenase enzyme (COX-1, COX-2 and COX-3) in arachidonic acid metabolism. This mechanism of COX-2 in carcinogenesis causes cancer. In addition, COX-2 plays a role in the early stages of hepatocarcinogenesis. Hepatitis C virus (HCV) infection is cause of liver cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to improve effective agents against HCV. A novel series of new etodolac 1,2,4-triazoles derivatives (4a-h) have been synthesized and investigated for their activity against HCV NS5B polymerase. Compound 4a was found to be the most active with IC50 value of 14.8 M. In accordance with these results, compound 4a was screened for anti-cancer activity on liver cancer cell lines (Huh7, Mahlavu, HepG2, FOCUS). Compound 4a showed anti-cancer activity against Huh7 human hepatoma cell line with IC50 value of 4.29 M. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound. © 2015 Informa UK Ltd.
Open Access
Cd81 Interacts with the T Cell Receptor to Suppress Signaling
(2012) Cevik, S.I.; Keskin, N.; Belkaya, S.; Ozlu, M.I.; Deniz, E.; Tazebay, U.H.; Erman, B.
CD81 (TAPA-1) is a ubiquitously expressed tetraspanin protein identified as a component of the B lymphocyte receptor (BCR) and as a receptor for the Hepatitis C Virus. In an effort to identify trans-membrane proteins that interact with the T-cell antigen receptor (TCR), we performed a membrane yeast two hybrid screen and identified CD81 as an interactor of the CD3delta subunit of the TCR. We found that in the absence of CD81, in thymocytes from knockout mice, TCR engagement resulted in stronger signals. These results were recapitulated in T cell lines that express low levels of CD81 through shRNA mediated silencing. Increased signaling did not result from alterations in the levels of TCR on the surface of T lymphocytes. Although CD81 is not essential for normal T lymphocyte development, it plays an important role in regulating TCR and possibly pre-TCR signal transduction by controlling the strength of signaling. CD81 dependent alterations in thymocyte signaling are evident in increased CD5 expression on CD81 deficient double positive (DP) thymocytes. We conclude that CD81 interacts with the T cell receptor to suppress signaling. © 2012 Cevik et al.
Open Access
Expression and purification of the hepatitis C virus core protein in Ecoli and testing of human sera with this core antigen
(1998) Eroğlu, Çağla
The hepatitis C virus (HCV) infection is an important cause of morbidity and mortality world wide. Infection with HCV becomes chronic in more than 80% of the cases and it accounts for 20%of all cases of acute hepatitis. Hepatitis C virus was first identified by the molecular cloning of the virus genome in 1989. It is an enveloped, positive strand RNA virus with a genome size of around 9.5 Idlobases. The single stranded RNA genome of the virus contains a large open reading frame codes for a large poly-protein of 3,010 to 3,033 amino acids which is shown to be processed by a combination of host and viral proteinases to produce at least ten proteins post-translationally. The proteins that are closer to the amino terminal of the poly-protein are termed as structural and the rest closer to the carboxy terminal are called non-structural (NS) proteins. The core protein is the putative nucleocapsid component of the virion, and it is highly basic in nature. Core protein is the most highly conserved region of the hepatitis C virus open reading frame and it is shown to be highly immunogenic. Also, as the core protein is the putative capsid protein of the hepatitis C virus, antibodies against core antigen most probably arise much earlier than the antibodies against nonstructural proteins. In this study, the core protein of the hepatitis C virus was cloned, expressed and purified in order to establish an ELISA system to test the human sera with this viral antigen. It was shown that in 86% of the patients, diagnosed previously with the third generation enzyme immunoassays to be infected with hepatitis C, have antibodies against this core antigen. The core antigen gave no false positive results when tested with the negative control samples which were found to be Anti-HCV negative previously.
Open Access
A highly sensitive and specific enzyme-linked immunosorbent assay of antibodies to hepatitis C virus
(2000) Eroğlu, C.; Yıldız, E.; Öztürk, M.; Pınarbaşı, E.
In this study, a 178 amino acids long portion of the hepatitis C virus (HCV) core gene was cloned, sequenced, expressed in Escherichia coli, and purified. The resulting antigen (C178) was tested with human sera enzyme-linked immunosorbent assay (ELISA) in order to assess its ability to diagnose HCV. It was shown by ELISA that 92% of the patients sera, diagnosed previously by a 3(rd) generation enzyme immunoassay (EIA) as HCV-positive, had antibodies against the C178 antigen. This antigen gave no false positive results when tested with anti-HCV-negative sera.
Open Access
Molecular characterization of a full genome Turkish hepatitis C virus 1b isolate (HCV-TR1): A predominant viral form in Turkey
(Kluwer Academic Publishers, 2002) Yıldız, E.; Oztan, A.; Sar, F.; Pınarbası, E.; Cetin Atalay, R.; Akkız, H.; Ozturk, M.
Based on direct sequencing information from 5′UTR and NS5B regions, we identified subtype 1b as a predominant hepatitis C virus genome in Turkey, which affected more than 91% of 79 patients studied. Next, the full genome sequence of a Turkish 1b isolate was obtained by the cloning of polypeptide-encoding region into 7 overlapping fragments. Turkish 1b isolate, which was named HCV-TR1, comprises 9361 nucleotides, including 306 nucleotides of 5′UTR, a single long open reading frame of 9033 nucleotides, and 22 nucleotides of 3′UTR. When compared to HCV 1b polypeptide sequences available at GenBank, the predicted polypeptide displayed a total of 36 amino acid substitutions, of which 16 was specific for HCV-TR1 isolate. Despite these changes, major structural and functional motifs of HCV proteins were maintained in HCV-TR1. In contrast, HCV-TR1 displayed amino acid substitutions in 6 out of 9 major cytotoxic T-cell epitopes. These data suggest that HCV-TR1 encodes functionally intact viral proteins, but it also encodes altered viral epitopes, which may affect host immune-response.
Open Access
PPAR-alpha L162V polymorphism in human hepatocellular carcinoma
(Turkish Society of Gastroenterology, 2008) Koytak, E. S.; Mızrak, D.; Bektaş, M.; Verdi, H.; Arslan-Ergül, Ayça; İdilman, R.; Çınar, K.; Yurdaydın, C.; Ersöz, S.; Karayalçın, K.; Uzunalimoğlu, Ö.; Bozkaya, H.
Background/aims: Several lines of evidence suggest that peroxisome proliferator-activated receptor alpha may be involved in hepatocarcinogenesis. L162V polymorphism of the peroxisome proliferator-activated receptor alpha gene enhances the transactivation activity of this transcription factor. The aim of this study was to determine the frequency and clinical correlates of peroxisome proliferator-activated receptor alpha L162V polymorphism in hepatitis virus-induced hepatocellular carcinoma. Methods: 90 hepatocellular carcinoma patients diagnosed at Ankara University Gastroenterology Clinic between January 2002 and July 2003 and 80 healthy controls with normal body mass index, blood chemistry and with negative viral serology were included. peroxisome proliferator-activated receptor alpha L162V polymorphism was determined by PCR-RFLP. Results: hepatocellular carcinoma etiologies were as follows: 56 HBV, 12 HBV+HDV, 22 HCV. Eighty-seven patients (97%) were cirrhotic, and 60 patients (67.5%) had advanced tumors. In 83 (92%) of 90 hepatocellular carcinoma patients, gene segment including polymorphic region could be amplified by PCR (50 HBV, 12 HBV+HDV, 21 HCV) and 6 of them (7.2%, all infected with HBV) had L162V polymorphism, while 2 (2.5%) of 80 controls had this polymorphism (p=0.162). This trend became more remarkable when only HBV (HBV+HDV)-infected patients were compared with controls (6/62, 9.7% vs. 2/80, 2.5%, respectively, p=0.071). Five of 6 patients with L162V had advanced disease. Conclusions: Peroxisome proliferator-activated receptor alpha L162V polymorphism tends to occur in HBV-induced epatocellular carcinoma and is absent in HCV-related epatocellular carcinoma. These findings may show clues for the existence of different carcinogenesis mechanisms in these two common etiologies. Frequent occurrence of advanced disease in patients with L162V polymorphism suggests a role for this polymorphism in tumor progression.