• Journal of Microbiology
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• v.43 no.6
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• pp.529-536
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• 2005

Viral infection causes stress to the endoplasmic reticulum (ER). The response to endoplasmic reticulum stress, known as the unfolded protein response (UPR), is designed to eliminate misfolded proteins and allow the cell to recover. The role of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV replicons that induce UPR, is incompletely understood. We demonstrate that HCV NS4B could induce activating transcription factor (ATF6) and inositol-requiring enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM (ER degradation-enhancing $\alpha-mannosidase-like$ protein, a protein degradation factor), was inhibited. These results imply that NS4B might induce UPR through ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or HCV subreplicon replication.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1705-1712
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• 2016

Background: The aim of this study was to determine and evaluate the association of different viral infections, with hepatitis B and C viruses, Epstein-Barr virus, cytomegalovirus and human herpes virus-8 (HBV, HCV, EBV, CMV, HHV-8) with the risk of lymphomas (Hodgkin and non-Hodgkin) among Egyptian patients, and correlate with the histopathological staging and typing as well as the prevalence of combined infections. Materials and Methods: A total of 100 newly diagnosed lymphoma patients with 100 healthy age and sex matched normal controls were assayed for viral infection using enzyme linked immunosorbant assay (ELISA) followed by real time polymerase chain reaction (RT-PCR). Results: Our results showed a high statistical significant difference between cases and controls as regards clinical and laboratory findings (P<0.001 and=0.003). A high statistical difference was seen for the association of most viruses and lymphoma cases (p<0.001) except for positive HBs Ag, positive CMV IgG and HHV-8 (p=0.37, 0.70 and 1.0 respectively). No statistical significant difference was found between Hodgkin (HL) and non-Hodgkin (NHL) as regards viral prevalence except HCV antigen, 57.1% for HL and 26.5% for NHL (p = 0.03). Only, HBV DNA showed a high significant value among infiltrated bone marrow cases (p=0.003) and finally, a high significant association of 2 combined viral infections with infiltrated bone marrow lymphoma cases (p=0.04). Conclusions: Our results showed that infection with HBV, HCV, CMV and EBV were associated with increased risk of lymphoma among the Egyptian population. Detection of new associations between infectious agents and risk of cancer development will facilitate progress in elaboration of prophylactic measures, early diagnostic methods and, hopefully, novel therapy of malignant tumours.

• The Journal of Korean Society of Virology
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• v.29 no.1
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• pp.45-53
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• 1999

We examined the hepatitis G virus infections among 227 Koreans who were healthy or were suspected of hepatitis and determined the phylogenetic relationship based on a part of the NS-5 region of 5 positive samples. Viral RNA was extracted from sera and cDNA was synthesized and subsequently amplified by RT-PCR (reverse transcription-polymerase chain reaction) or RT-nested PCR using random hexamer and NS-5 specific primers (470-20-1-77F, 470-20-1-211R, HGVNESTFO, HGVNESTRE). Five positives were found to belong to samples of patients showing symptoms of viral hepatitis. Primers used for PCR or nested PCR were derived from the NS-5 region. On the other hand, no amplification was detected using primers derived from the 5'-NCR (G-146F, G-401R). We performed TA cloning and sequencing of 5 amplified fragments, and their sequences were compared with those of foreign isolates of HGV. The phylogenetic analysis using MegAlign programme of DNAstar has shown that the Korean isolates are clustered on the phylogenetic tree. In summary, we confirmed the hepatitis G virus infection in 5 cases out of 12 patients showing the symptoms of viral hepatitis. The phylogenetic analysis of sequences of 5 amplified fragments showed that their relations to each other were closer than those to the foreign HGV isolates reported.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.8 no.2
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• pp.202-212
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• 2005

Purpose: Transfusion transmitted virus (TTV) is a newly discovered virus and to date the contribution of TTV to liver disease remains unclear. Little is known about the frequency of TTV infection in children in Korea. The purpose of this study was to investigate the prevalence and genotypic distribution of TTV carried by healthy children and patients with hepatitis in Korea. Methods: Eighty eight of healthy children and three groups of patients with hepatitis-14 patients with chronic hepatitis B, 12 patients with chronic hepatitis C and 25 patients with hepatitis of unknown etiology-were tested. TTV DNA was detected by semi-nested PCR using primer sets generated from N-22 region and from 5' noncoding region (NCR) of the viral genome. PCR products derived from 8 patients with hepatitis and from 11 healthy children were sequenced and a phylogenetic tree was constructed. Results: TTV was found by PCR with N22 primer in 11.3% of healthy children, 28.5% of children with hepatitis B, 25% of children with hepatitis C, 24% of children with hepatitis of unknown etiology. TTV DNA was found by PCR with 5'NCR primer in 32.9% of healthy children, 71.4% of patients with chronic hepatitis B, in 50% of patients with hepatitis C and in 48% of patients with hepatitis of unknown etiology. TLMV DNA was found in 48.9% of healthy children, 21.4% of patients with hepatitis B, 16.6% of patients with hepatitis C, 40% of patients with hepatitis of unknown etiology. Among the sequenced isolates, 10(52%) belonged to genotype 1 (G1) and others belonged to genotype 2 (G2) or genotype 3 (G3). Among the G1 sequences, 7 were grouped as G1a. Conclusion: TTV infection was common in healthy children and in patients with hepatitis. But, the prevalence of TTV DNA by 5'NCR primer was relatively high in patients with hepatitis B and there may be some association between TTV and hepatitis B virus infection. G1 was the major genotype of the studied population.

• Archives of Pharmacal Research
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• v.29 no.6
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• pp.431-458
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• 2006

As we approach the completion of the first 25 years of the human immunodeficiency virus(HIV) epidemic, there have been dramatic improvements in the care of patients with HIV infection. These have prolonged life and decreased morbidity. There are twenty currently available antiretrovirals approved in the United States for the treatment of this infection. The medications, including their pharmacokinetic properties, side effects, and dosing are reviewed. In addition, the current approach to the use of these medicines is discussed. We have included a section addressing common comorbid conditions including hepatitis B and C along with tuberculosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7213-7218
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• 2014

Background: Egypt has one of the highest prevalences of hepatitis C virus (HCV) infection worldwide. Although the IL28B gene polymorphism has been shown to modify the course of chronic HCV infection, this has not been properly assessed in the Egyptian population. Materials and Methods: The IL28B rs12979860 single nucleotide polymorphism (SNP) was therefore examined in 256 HCV-infected Egyptian patients (group II) at different stages of disease progression and in 48 healthy volunteers (group I). Group II was subdivided into GII-A (chronic hepatitis patients, n=119), GII-B (post hepatitis cirrhosis, n=66) and GII-C (HCC on top of cirrhosis, n=71). Results: The C/T genotype was the commonest in all groups. It was more frequent in GI (52%) than in GII (48%). There was no significant difference in the frequency of C/T and C/C or T/T genotypes between groups and subgroups (p=0.82). Within the subgroups; the C/C genotype was more common in GII-B while C/T and T/T genotypes were more common in GII-C, though with no significant difference (p=0.59 and p=0.80). There was no significant association between IL28B rs12979860 SNP and viral load, ALT, AFP level, METAVIR scores for necro-inflammation and fibrosis, and Child-Pugh classification. Conclusions: 1) IL28Brs12979860 C/T genotype is the commonest genotype in HCV-associated CH and HCC in Egypt. 2) IL28Brs12979860 polymorphisms are not associated with disease progression or aggression (histological staging, severity of fibrosis in CH or the incidence of post-HCV HCC). 3) Differences in IL28Brs12979860 genotypes could be a consequence of environmental or ethnic variation.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.1
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• pp.28-37
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• 2022

Pregnancy requires an important interpretation of thyroid function tests. The presence of anti-thyroid antibodies and viral infectious agents affect the health of both the fetus and the mother. Hence, a selective evaluation of thyroid function in pregnancy is required. This study is a retrospective cross-sectional survey to examine the correlation between thyroid hormones and viral infections during pregnancy. The results showed that the triiodothyronine (T3) decreased with increasing age, especially in the hepatitis C virus (HCV)-positive group (P<0.01). In addition, although negative for the human immunodeficiency virus (HIV), thyroxine (FT4) showed a significant increase in near-threshold or twin pregnant women (P<0.05). The thyroid stimulating hormone (TSH) was highly distributed at the age of 30, and there was no statistically significant correlation with other viral infection factors. In addition, as a result of dividing and analyzing the result of TSH by the quantiles, FT4 and T3 showed a positive correlation but showed a negative correlation with TSH (P<0.05). Therefore, the evaluation of prenatal thyroid screening during pregnancy and viral infection factors should reflect the time of pregnancy, exposure to infection, and the quantitative values. Adequate thyroid hormone and viral infections availability is important for an uncomplicated pregnancy and optimal fetal development.

• Korean Journal of Clinical Pharmacy
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• v.27 no.3
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• pp.150-160
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• 2017

Background: Recently, a fixed combination of grazoprevir and elbasvir (GE) has been introduced to the arsenal of chemotherapeutics to fight against this virus. The study aimed to provide information on the efficacy and safety of GE for the treatment of HCV infection by performing a meta-analysis of literature data. Methods: PubMed and EMBASE database searches were conducted. Among the literature retrieved, pivotal Phase III clinical studies were analyzed. Statistical analysis of the data was performed by RevMan. Results: Four pivotal Phase III clinical studies compared the efficacy and safety of GE. When HCV patients were treated with GE for 12 weeks, the sustained virologic response, defined as the viral RNA level below the lower limit of quantification at 12 weeks after the cessation of therapy (SVR12), was 94.7%. The clinical advantage of GE involves its use by patients with cirrhosis and/or renal failure without dose adjustment. If the genotype (GT) of the causative virus was GT1a with NS5A polymorphism or GT4 with resistance to peginterferon/ribavirin, treatment with GE plus ribavirin for 16 weeks resulted in a better outcome compared to treatment with GE alone for 12 weeks. Adverse events reported during the four clinical studies were 71.09% in the GE arms and it was 76.61% in the non-GE arms, with the most frequent events being mild central nervous system symptoms. Conclusion: GE was generally safe and effective for the treatment of HCV infection. However, since HCV mutates very rapidly and becomes resistant to antiviral agents, long-term monitoring should be mandatory.

• Journal of Microbiology and Biotechnology
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• v.16 no.10
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• pp.1634-1639
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• 2006

Hepatitis C virus (HCV)-encoded nonstructural protein 5B (NS5B) possesses RNA-dependent RNA polymerase activity, which is considered essential for viral proliferation. Thus, HCV NS5B is a good therapeutic target protein for the development of anti-HCV agents. In this study, we isolated two different kinds of nuclease-resistant RNA aptamers with 2'-fluoro pyrimidines against the HCV NS5B from a combinatorial RNA library with 40 nucleotide random sequences, using SELEX technology. The isolated RNA aptamers were observed to specifically and avidly bind the HCV NS5B with an apparent $K_d$ of 5 nM and 18 nM, respectively, in contrast with the original RNA library that hardly bound the target protein. Moreover, these aptamers could partially inhibit RNA synthesis of the HCV subgenomic replicon when transfected into Huh-7 hepatoma cell lines. These results suggest that the RNA aptamers selected in vitro could be useful not only as therapeutic agents of HCV infection but also as a powerful tool for the study of the HCV RNA-dependent RNA polymerase mechanism.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.637-642
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• 2014

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.