• Journal of Microbiology
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• 제43권6호
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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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• 제17권4호
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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.

• 대한바이러스학회지
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• 제29권1호
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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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• 제8권2호
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• pp.202-212
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• 2005

목 적: Transfusion-transmitted virus는 간염과의 연관성이 아직 명확하지 않지만 특정 유전형이 원인불명의 간염 병원체로 작용하거나 다른 간염 바이러스와 중복 감염되어 임상 경과에 영향을 줄 가능성에 대한 연구가 필요하다. 본 연구는 국내 소아 B형 간염, C형 간염 및 원인 불명의 간염 환자의 TTV DNA 양성률과 유전형의 분포를 알아보기 위해 시행하였다. 방 법: 간 기능이 정상인 소아 88명을 대조군으로 하였으며 B형 간염 환자 14명, C형 간염 환아 12명, 2001년 6월부터 2004년 6월까지 인제의대 상계백병원을 방문한 원인 불명의 간염 환자 25명을 대상으로 하였다. 환아의 혈청 검체를 대상으로 N22 시발체를 이용한 PCR과 5'NCR 시발체를 이용한 PCR을 시행하였다. 또한 TLMV DNA 검출을 위한 seminested PCR을 시행 하였다. N22 primer를 이용한 PCR 양성 산물을 대상으로 염기서열의 직접 분석이 시행되었다. 결 과: 1) N22 시발체를 이용한 TTV DNA 양성률은 대조군에서 11.3%, 간염군에서 19.6%였다(p=0.105). B형 간염의 28.5%, C형 간염의 25%, 원인 불명의 간염 24%에서 TTV DNA가 양성이었으며 대조군에 비해 유의한 차이는 없었다. 2) 5'NCR 부위 시발체를 이용한 TTV DNA 양성률은 대조군에서 32.9%, 간염군에서 54.9%였다. B형 간염의 71.4%, C형 간염의 50%, 원인 불명의 간염 48%에서 TTV DNA가 양성이었다. B형 간염 환자군에서 양성률이 대조군에 비해 높았다(p=0.008). 3) 5'NCR 부위 시발체를 이용한 TLMV DNA양성률은 간염 환자군과 정상 대조군에서 각각 29.4% (15/51명), 48.9% (43/88명)였다. B형 간염 21.4% (3/14), C형 간염 16.6% (2/12), 원인 불명의 간염 환자에서 40% (10/25)였다. 4) 염기 서열 분석: N22 시발체를 이용해서 PCR 반응 산물 중 총 29예(간염 환자 8명, 대조군 11명)의 염기서열을 분석한 결과 G1 유전형은 10예(52%)였고 이 중 G1a형이 7예였다. G2 유전형은 3예, G3 유전형은 2예였으며 나머지는 정확한 분류가 되지 않았다. 결 론: 국내 소아에 감염된 TTV 유전형 중 가장 흔한 것은 G1형이었다. TTV DNA 양성률은 대조군과 원인 불명의 간염군 간에 차이는 없었으며, B형 간염군에서 대조군에 비해 높았다.

• Archives of Pharmacal Research
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• 제29권6호
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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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• 제15권17호
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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.

• 대한임상검사과학회지
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• 제54권1호
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• pp.28-37
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• 2022

임신은 갑상선 기능 검사의 중요한 해석을 필요로 하며 임신 중 갑상선 기능 이상과 외부 바이러스성 감염 인자들의 항체의 존재는 태아 및 산모의 건강에 영향을 미치기에 임신에서 갑상선 기능의 선별적 평가가 요구된다. 본 연구에서는 임신기간 동안 정상 산모들의 선택적 산전 감염인자 검사 항목 중에서 갑상선 관련 인자와 바이러스성 감염 인자의 임신시기별 상호 연관성을 알아보고자 하는 후향적 단편 실태조사이다. 분석한 결과를 살펴보면, T3는 나이가 증가함에 따라 감소하고, 특히 HCV가 양성인 그룹에서 양의 유의성을 보였다(P<0.01). 또한 HIV가 음성이지만 임계치에 근접하거나 쌍둥이 임산부에서는 FT4가 유의한 증가를 나타냈다(P<0.05). TSH는 30대 연령에서 높게 분포하였으며, 다른 바이러스성 감염인자와는 통계적 유의성이 나타나지 않았다. 또한, TSH의 결과 값을 삼분위로 나누어 분석한 결과, FT4와 T3은 양의 상관성을 보였으나 TSH와는 음의 상관성을 보였다(P<0.05). 따라서 본 연구를 통해서 임신 중 산전검사인 갑상선 검사와 바이러스성 감염인자의 검사를 통한 임신 중 평가는 임신 경과시간, 감염인자의 노출상태 및 정량적 수치의 상태를 반영하여 이루어져야 할 것이며, 갑상선 관련 내분비 인자에 대한 산전검사의 유용성에 대한 평가의 보완이 이루어져야 할 것으로 사료된다.

• 한국임상약학회지
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• 제27권3호
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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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• 제16권10호
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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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• 제15권2호
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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.