• 제목/요약/키워드: HCV (Hepatitis C virus)

검색결과 152건 처리시간 0.024초

활막 세포에서 HCV Core 단백에 의한 Interleukin-8 발현 유도 (Induction of Interleukin-8 Expression in Synovial Cell by Hepatitis C Virus Core Protein)

  • 왕진상;허원희;김소연;윤승규
    • IMMUNE NETWORK
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    • 제6권1호
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    • pp.20-26
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    • 2006
  • Background: Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease that is characterized by invasive synovial hyperplasia, leading to progressive joint destruction. Recent studies have described that RA is caused by virus, bacteria or outside material. Approximately 2 to 20% of RA cases arc reported to be associated with infected hepatitis C virus (HCV). However, the mechanisms underlying virus-induced RA are still unknown. Moreover, few molecular studies have addressed the inflammatory aspects of HCV-associated autoimmune RA. In this study, we aimed to determine whe ther or not another HCV core protein transactivates the IL-8 gene expression, prototypic chemokine, in synovial cell. Methods: To establish the HCV core expressing stable synovial cell line, pCI-neo-core, a plasmid encoding HCV core protein, were transfected to HIG-82 cell line that is an established cell line from rabbit periaricular soft tissue. We examined the morphological changes and cell cycle distribution of HIG-82 cells with expression of HCV core protein by inverted microscopy and flow cytometry analysis, respectively. Also, we determined the mRNA levels of Interleukin (IL)-6 and IL-8 related to the inflammation by RT-PCR and then analyzed regulation of IL-8 expression by the NF-${\kappa}B$ pathway. Results: Our study showed no significant differences in morphology and cell cycle between HIG-82 control cell line and HIG-82 expressing HCV core protein. However, expression of HCV core protein induces the IL-8 mRNA expression in HIG-82 core cells via activated NF-${\kappa}B$ pathway. Conclusion: These results suggest that HCV core protein can lead to enhanced IL-8 expression. Such a proinflammatory role may contribute to the etiologic pathogenesis in RA patients with HCV infection.

Hepatitis C Viral Infection in Children: Updated Review

  • El-Guindi, Mohamed A.
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제19권2호
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    • pp.83-95
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    • 2016
  • Hepatitis C virus (HCV) infection is a major medical challenge affecting around 200 million people worldwide. The main site of HCV replication is the hepatocytes of the liver. HCV is a positive enveloped RNA virus from the flaviviridae family. Six major HCV genotypes are implicated in the human infection. In developed countries the children are infected mainly through vertical transmission during deliveries, while in developing countries it is still due to horizontal transmission from adults. Minimal nonspecific and brief symptoms are initially found in approximately 15% of children. Acute and chronic HCV infection is diagnosed through the recognition of HCV RNA. The main objective for treatment of chronic HCV is to convert detected HCV viremia to below the detection limit. Children with chronic HCV infection are usually asymptomatic and rarely develop severe liver damage. Therefore, the benefits from current therapies, pegylated-Interferon plus ribavirin, must be weighed against their adverse effects. This combined treatment offers a 50-90% chance of clearing HCV infection according to several studies and on different HCV genotype. Recent direct acting antiviral (DAA) drugs which are well established for adults have not yet been approved for children and young adults below 18 years. The most important field for the prevention of HCV infection in children would be the prevention of perinatal and parenteral transmission. There are areas of focus for new lines of research in pediatric HCV-related disease that can be addressed in the near future.

Interaction of Hepatitis C Virus Core Protein with Janus Kinase Is Required for Efficient Production of Infectious Viruses

  • Lee, Choongho
    • Biomolecules & Therapeutics
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    • 제21권2호
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    • pp.97-106
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    • 2013
  • Chronic hepatitis C virus (HCV) infection is responsible for the development of liver cirrhosis and hepatocellular carcinoma. HCV core protein plays not only a structural role in the virion morphogenesis by encapsidating a virus RNA genome but also a non-structural role in HCV-induced pathogenesis by blocking innate immunity. Especially, it has been shown to regulate JAK-STAT signaling pathway through its direct interaction with Janus kinase (JAK) via its proline-rich JAK-binding motif ($^{79}{\underline{P}}GY{\underline{P}}WP^{84}$). However, little is known about the physiological significance of this HCV core-JAK association in the context of the virus life cycle. In order to gain an insight, a mutant HCV genome (J6/JFH1-79A82A) was constructed to express the mutant core with a defective JAK-binding motif ($^{79}{\underline{A}}GY{\underline{A}}WP^{84}$) using an HCV genotype 2a infectious clone (J6/JFH1). When this mutant HCV genome was introduced into hepatocarcinoma cells, it was found to be severely impaired in its ability to produce infectious viruses in spite of its robust RNA genome replication. Taken together, all these results suggest an essential requirement of HCV core-JAK protein interaction for efficient production of infectious viruses and the potential of using core-JAK blockers as a new anti-HCV therapy.

Hepatitis C Virus - Proteins, Diagnosis, Treatment and New Approaches for Vaccine Development

  • Keyvani, Hossein;Fazlalipour, Mehdi;Monavari, Seyed Hamid Reza;Mollaie, Hamid Reza
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권12호
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    • pp.5917-5935
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    • 2012
  • Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infection and as such is an important global health problem. The virus was discovered in the USA in 1989 and it is now known that three to four million people are infected every year, WHO estimating that 3 percent of the 7 billion people worldwide being chronically infected. Humans are the natural hosts of HCV and this virus can eventually lead to permanent liver damage and carcinoma. HCV is a member of the Flaviviridae family and Hepacivirus genus. The diameter of the virus is about 50-60 nm and the virion contains a single-stranded positive RNA approximately 10,000 nucleotides in length and consisting of one ORF which is encapsulated by an external lipid envelope and icosahedral capsid. HCV is a heterogeneous virus, classified into 6 genotypes and more than 50 subtypes. Because of the genome variability, nucleotide sequences of genotypes differ by approximately 31-34%, and by 20-23% among subtypes. Quasi-species of mixed virus populations provide a survival advantage for the virus to create multiple variant genomes and a high rate of generation of variants to allow rapid selection of mutants for new environmental conditions. Direct contact with infected blood and blood products, sexual relationships and availability of injectable drugs have had remarkable effects on HCV epidemiology. Hundreds of thousands of people die each year from hepatitis and liver cancer caused by HCV virus infection. Approximately 80% of patients with acute hepatitis C progress into a chronic disease state leading to serious hepatic disorders, 10-20% of which develop chronic liver cirrhosis and hepatocellular carcinoma. The incubation period of HCV is 6-8 weeks and the infection is often asymptomatic so it is very hard to detect at early stages, making early treatment very difficult. Therefore, hepatitis C is called a "silent disease". Neutralizing antibodies are produced against several HCV proteins during infection but the virus mutates to escape from antibodies. Some patients with chronic hepatitis C may have some symptoms such as fatigue, muscle aches, nausea and pain. Autoimmune and immunecomplex-mediated diseases have also been reported with chronic HCV infection.

C형 간염바이러스(HCV)의 NS5B RNA Replicase에 의해 활성이 유도되는 Hammerhead 리보자임에 의한 HCV 복제 억제 연구 (Inhibition of Hepatitis C Virus (HCV) Replication by Hammerhead Ribozyme Which Activity Can Be Allosterically Regulated by HCV NS5B RNA Replicase)

  • 이창호;이성욱
    • 미생물학회지
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    • 제47권3호
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    • pp.188-193
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    • 2011
  • C형 간염바이러스(hepatitis C virus; HCV) 증식을 효과적이며 특이적으로 제어할 수 있는 유전산물로서, HCV 증식조절인자인 NS5B RNA replicase 존재에 의해 allosteric하게 활성이 유도될 수 있는 HCV internal ribosome entry site (IRES) 표적 hammerhead 리보자임을 개발하였다. 이러한 리보자임은 HCV IRES 염기서열 중 +382 nucleotide 자리를 인지하는 hammerhead 리보자임, NS5B RNA replicase와 특이적으로 결합하는 RNA aptamer 부위, 그리고 aptamer와 NS5B와의 결합에 의해 리보자임 활성을 유도할 수 있도록 구조적 변이를 전달할 수 있는 communication module 부위 등으로 구성되어 있다. 이러한 allosteric 리보자임에 의해 세포 배양에서 HCV의 replicon 복제가 효과적으로 억제됨을 실시간 PCR 분석을 통하여 관찰하였다. 특히, HCV 지놈을 표적하는 리보자임 단독, 또는 HCV NS5B에 대한 RNA aptamer 단독에 의한 HCV 복제 억제능보다 allosteric 리보자임에 의한 HCV 복제 억제능이 더 뛰어났다. 따라서 개발된 allosteric 리보자임은 HCV 증식의 효과적인 증식 억제 선도물질로 활용될 수 있을 것이다.

Cyclophilin A as a New Therapeutic Target for Hepatitis C Virus-induced Hepatocellular Carcinoma

  • Lee, Jinhwa
    • The Korean Journal of Physiology and Pharmacology
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    • 제17권5호
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    • pp.375-383
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    • 2013
  • Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.

Hepatitis C Virus Core Protein Is Efficiently Released into the Culture Medium in Insect Cells

  • Choi, Soo-Ho;Kim, So-Yeon;Park, Kyu-Jin;Kim, Yeon-Joo;Hwang, Soon-Bong
    • BMB Reports
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    • 제37권6호
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    • pp.735-740
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    • 2004
  • Hepatitis C virus (HCV) is a causal agent of the chronic liver infection. To understand HCV morphogenesis, we studied the assembly of HCV structural proteins in insect cells. We constructed recombinant baculovirus expression vectors consisting of either HCV core alone, core-E1, or core-E1-E2. These structural proteins were expressed in insect cells and were examined to assemble into particles. Neither core-E1 nor core-E1-E2 was capable of assembling into virus-like particles (VLPs). It was surprising that the core protein alone was assembled into core-like particles. These particles were released into the culture medium as early as 2 days after infection. In our system, HCV structural proteins including envelope proteins did not assemble into VLPs. Instead, the core protein itself has the intrinsic capacity to assemble into amorphous core-like particles. Furthermore, released core particles were associated with HCV RNA, indicating that core proteins were assembled into nucleocapsids. These results suggest that HCV may utilize a unique core release mechanism to evade the hosts defense mechanism, thus contributing to the persistence of HCV infection.

Expression and Characterization of Hepatitis C Virus Core Proteins: Effects of Single Amino Acid Substitution on Protein Conformation and Subcellular Localization

  • Hwang, Soon-Bong
    • BMB Reports
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    • 제31권3호
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    • pp.281-286
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    • 1998
  • Hepatitis C virus (HCV) core proteins from two different isolates (HCV-1 and HCV-RH) were expressed in Spotioptera Jrugiperda (Sf9) insect cells. The RH core consisted of two major species of proteins (21 kDa and 19 kDa). On the other hand, the HCV-1 core was approximately 16 kDa in a SDS-PAGE gel. Both core proteins were phosphorylated in vivo on serine residues. Furthermore, the RH core but not HCV-1 core formed dimers, indicating that the protein conformation of the core in these two isolates is dfferent from one another. Immunofluorescence studies showed that the RH core was present in the cytoplasm, whereas the HCV-1 core was localized predominantly to the nucleus in recombinant baculovirus-infected insect cells. Since the major difference between the two isolates is the codon 9 of the core protein, a single amino acid substitution appears to play a major role in the protein conformation and these properties may reflect the different biological functions of core proteins in HCV-infected cells.

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C형 간염 산모로부터 출생한 영아에서 C형 간염 Virus의 수직 전파 1례 (A Case of Vertical Transmission of Hepatitis C Virus in an Infant of a Mother Who had Hepatitis C during Pregnancy)

  • 오상현;김국환;양은석;박상기;문경래
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제2권1호
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    • pp.109-115
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    • 1999
  • Hepatitis C virus (HCV) has been identified as an important cause of posttransfusion hepatitis, but vertical transmission of chronic infected HCV RNA positive mothers has been documented in some cases. The reports of the risk of perinatal infection have been widely varied in the literature. The authors experienced one case of vertical transmission of HCV in an infant of a mother who had hepatitis C during pregnancy. At admission, HCV RNA (+), Ig G anti HCV (+) and Ig M anti HCV (+) were found in the mother. Also at admission, HCV RNA (+), Ig G anti HCV (+), Ig M anti HCV (+), elevation of liver aminotransferase level and hepatosplenomegaly on ultrasonography were found in the baby on day 31. HCV RNA (-), Ig M anti HCV (-) and normal of liver aminotransferase level were noted on day 250 in the serum of the infant. We used reverse transcriptase polymerase chain reaction (RT-PCR) technique to find a very small amount of HCV RNA in the serum. All the findings suggest vertical transmission of HCV RNA from mother to infant during 3rd trimester of pregnancy.

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Induction of Cytotoxic T Lymphocyte Response against the Core and NS3 Genes of the Hepatitis C Virus in Balb/c Mice

  • Kim, Na-Young;Sohn, He-Kwang;Choe, Joon-Ho;Park, Sang-Dai;Seong, Rho-Hyun
    • Animal cells and systems
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    • 제3권3호
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    • pp.337-341
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    • 1999
  • Hepatitis C virus (HCV) is a positive strand RNA virus of the Flaviviridae family and the major cause of post-transfusion non-A, non-B hepatitis. Vaccine development for HCV is essential but has been slowed by poor understanding of the type of immunity that naturally terminates HCV infection. The DNA-based immunization technique offers the potential advantage of including cellular immune responses against conserved internal proteins of a virus, as well as the generation of antibodies to viral surface proteins. Here, we demonstrate that cell lines expressing the HCV core and/or NS3 proteins can induce a specific CTL response in mice, and these results suggest a possibility that the HCV core and NS3 DNA can be used to induce CTL activity against the antigen in mice and can be further developed as a therapeutic and preventive DNA vaccine.

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