• IMMUNE NETWORK
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• 제14권4호
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• pp.207-218
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• 2014

Chronic virus infection leads to the functional impairment of dendritic cells (DCs) as well as T cells, limiting the clinical usefulness of DC-based therapeutic vaccine against chronic virus infection. Meanwhile, B cells have been known to maintain the ability to differentiate plasma cells producing antibodies even during chronic virus infection. Previously, ${\alpha}$-galactosylceramide (${\alpha}GC$) and cognate peptide-loaded B cells were comparable to DCs in priming peptide-specific $CD8^+$ T cells as antigen presenting cells (APCs). Here, we investigated whether B cells activated by ${\alpha}GC$ can improve virus-specific T cell immune responses instead of DCs during chronic virus infection. We found that comparable to B cells isolated from naïve mice, chronic B cells isolated from chronically infected mice with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) after ${\alpha}GC$-loading could activate CD1d-restricted invariant natural killer T (iNKT) cells to produce effector cytokines and upregulate co-stimulatory molecules in both naïve and chronically infected mice. Similar to naïve B cells, chronic B cells efficiently primed LCMV glycoprotein (GP) 33-41-specific P14 $CD8^+$ T cells in vivo, thereby allowing the proliferation of functional $CD8^+$ T cells. Importantly, when ${\alpha}GC$ and cognate epitope-loaded chronic B cells were transferred into chronically infected mice, the mice showed a significant increase in the population of epitope-specific $CD8^+$ T cells and the accelerated control of viremia. Therefore, our studies demonstrate that reciprocal activation between ${\alpha}GC$-loaded chronic B cells and iNKT cells can strengthen virus-specific T cell immune responses, providing an effective regimen of autologous B cell-based therapeutic vaccine to treat chronic virus infection.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.275-279
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• 2013

Objectives: A number of studies have shown that chronic hepatitis B virus infection is implicated in susceptibility to pancreatic cancer. However, the results are still controversial. This meta-analysis aimed to quantitatively assess the relationship between chronic hepatitis B virus infection and incidence of pancreatic cancer of cohort and case-control studies. Methods: A literature search was performed for entries from 1990 to 2012 using PUBMED and EMBASE. Studies were included if they reported odds ratios (ORs) and corresponding 95% CIs of pancreatic cancer with respect to the infection of hepatitis B virus. Results: Eight studies met the inclusion criteria, which included five case-control studies and three cohort studies. Compared with individuals who have not infection of hepatitis B virus, the pooled OR of pancreatic cancer was 1.403 (95%CI: 1.139-1.729, P=0.001) for patients with hepatitis B virus infection. Sub-group analysis by study design showed that the summary OR was 1.43 (95%CI: 1.06-1.94, P=0.021) when pooling case-control studies and 1.31 (95%CI: 1.00-1.72, P=0.05) when pooling cohort studies. Conclusion: Findings from this meta-analysis suggest that chronic hepatitis B virus infection may increase the risk of pancreatic cancer. This relationship needs to be confirmed by further follow-up studies.

• IMMUNE NETWORK
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• 제20권1호
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• pp.2.1-2.19
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• 2020

Acute viral infection or vaccination generates highly functional memory CD8 T cells following the Ag resolution. In contrast, persistent antigenic stimulation in chronic viral infection and cancer leads to a state of T-cell dysfunction termed T-cell exhaustion. We and other have recently identified a novel subset of exhausted CD8 T cells that act as stem cells for maintaining virus-specific CD8 T cells in a mouse model of chronic lymphocytic choriomeningitis virus infection. This stem cell-like CD8 T-cell subset has been also observed in both mouse and human tumor models. Most importantly, in both chronic viral infection and tumor models, the proliferative burst of Ag-specific CD8 T cells driven by PD-1-directed immunotherapy comes exclusively from this stem cell-like CD8 T-cell subset. Therefore, a better understanding of the mechanisms how CD8 T-cell subsets are regulated during chronic viral infection and cancer is required to improve the current immunotherapies that restore the function of exhausted CD8 T cells. In this review, we discuss the differentiation of virus-specific CD8 T cells during chronic viral infection, the characteristics and function of CD8 T-cell subsets, and the therapeutic intervention of PD-1-directed immunotherapy in cancer.

• Annals of Clinical Neurophysiology
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• 제19권1호
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• pp.50-53
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• 2017

An infection is less likely to elicit chronic inflammatory demyelinating polyneuropathy (CIDP) than Guillain-$Barr{\acute{e}}$ syndrome. We here report a case of acute-onset CIDP following hepatitis A virus infection and briefly comment on the potential mechanisms regarding the induction and chronicity of autoimmunity after a viral infection.

• IMMUNE NETWORK
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• 제10권4호
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• pp.120-125
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• 2010

Dysfunction of the virus-specific T cells is a cardinal feature in chronic persistent viral infections such as one caused by hepatitis C virus (HCV). In chronic HCV infection, virus-specific dysfunctional CD8 T cells often overexpress various inhibitory receptors. Programmed cell death 1 (PD-1) was the first among these inhibitory receptors that were identified to be overexpressed in functionally impaired T cells. The roles of other inhibitory receptors such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) have also been demonstrated in T-cell dysfunctions that occur in chronic HCV patients. Blocking these inhibitory receptors in vitro restores the functions of HCV-specific CD8 T cells and allows enhanced proliferation, cytolytic activity and cytokine production. Therefore, the blockade of the inhibitory receptors is considered as a novel strategy for the treatment of chronic HCV infection.

• 미생물과산업
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• 제13권3호
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• pp.3-11
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• 1987

Hepatitis B virus (HBV) is a very serious threat to public health in most of the developing countries of the world. It is estimated that around 300 million people worldwide are chronic carriers of this virus and will transmit the disease both vertically and horizontally. Infection by this virus may cause a wide range of clinical manifestations ranging from an asymptomatic infection to liver cirrhosis.

• 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.

• Journal of Preventive Medicine and Public Health
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• 제19권2호
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• pp.281-292
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• 1986

Infection by hepatitis B virus is one of the major health problems of this nation. HBsAg positive rates of general population and school children were known to be as about 8 percent and 3.9 to 5.9 percent respectively. To study the incidence rate of hepatitis B infection in school children of rural area, author had examined 475 school children of relatively isolated agricultural area for baseline prevalence of hepatitis B virus serologic markers and followed up 415 school children during 10 months to determined the frequency of serologic conversion. The major results are summarized as followings: 1) Among the 278 susceptible children who were followed up, 26 had seroconversion for HBsAg or Anti-HBs. Therefore, the cumulative incidence rate during 10 months is estimated 9.4%. 2) The incidence rate of hepatitis B infection tends to increase with age (6-9yrs: 3.2%, 10-14yrs: 9.5%, 15-17yrs: 18.9%), and the incidence rate in male (13.0%) was higher than in female (5.7%). 3) The incidence rates of hepatitis B virus infection were not different statistically among three economic classes (The rates of lower, middle and higher class were 11.8%, 7.1% and 10.5%.). 4) The incidence rates of hepatitis B virus infection were not different statistically between visitors and non-visitors of clinic or hospital, dental clinic, persons received IV and not received IV, and persons with familial history and without familial history of liver diseases. Therefore all of these factors were not identified as risk factor of hepatitis B virus infection. And the transmissibility within the class of school was not recognized, too. 5) Among the 25 children who were HBsAg positive when enrolled, 15 (60%) were still HBsAg positive, who were identified as chronic carrier 15 of 415 school children were chronic carriers, then chronic carrier rate was estimated 3.6%, and there was no difference between sexes. 6) Of 38 children who had been Anti-HBs positive when enrolled, 5 (13.2%) lost Anti-HBs. Therefore, the loss rate of Anti-HBs per year is estimated to be 15.8%.

• 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.

• IMMUNE NETWORK
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• 제23권4호
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• pp.30.1-30.18
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• 2023

About 0.8 million people die because of hepatitis B virus (HBV) infection each year. In around 5% of infected adults, the immune system is ineffective in countering HBV infection, leading to chronic hepatitis B (CHB). CHB is associated with hepatocellular carcinoma, which can lead to patient death. Unfortunately, although current treatments against CHB allow control of HBV infection, they are unable to achieve complete eradication of the virus. Cytokines of the IFN family represent part of the innate immune system and are key players in virus elimination. IFN secretion induces the expression of interferon stimulated genes, producing proteins that have antiviral properties and that are essential to cell-autonomous immunity. IFN-α is commonly used as a therapeutic approach for CHB. In addition, IFN-γ has been identified as the main IFN family member responsible for HBV eradication during acute infection. In this review, we summarize the key evidence gained from cellular or animal models of HBV replication or infection concerning the potential anti-HBV roles of IFN-γ with a particular focus on some IFN-γ-inducible genes.