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      Comparison of ISG15, IL28B and USP18 mRNA levels in peripheral blood mononuclear cells of chronic hepatitis B virus infected patients and healthy individuals

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          Abstract

          Aim:

          The purpose of this study was to evaluate the expression level of Interferon-stimulated Gene 15 (ISG15), Interleukin28B (IL28B) or IFN-lambda-3 and Ubiquitin specific peptidase 18 (USP18) genes in Peripheral Blood Mononuclear Cells (PBMCs) of patients with chronic active and inactive hepatitis B in comparison with healthy individuals.

          Background:

          Despite the presence of the vaccine for hepatitis B virus (HBV), it remains a public health challenge. The effort to uncover the immune genes attributed to infection outcome is going through.

          Methods:

          This Cross-sectional study was conducted on hepatitis B infected patients that were admitted to the Clinic of Liver diseases, Shiraz, January-November 2016. Patients were divided into two groups including active and inactive chronic regarding relevant World Gastroenterology Organization Global Guideline. They were mono-infected with HBV, and HCV or HIV co-infection was excluded from the study. Gene expression analysis was performed on fresh PBMCs samples with the help of Real-time PCR method.

          Results:

          Interleukin 28B gene expression showed no statistically significant difference between the three studied groups (P>0.05). The expression level of ISG15 was significantly higher in the healthy control group compared to active (P= 0.0068) and inactive chronic subjects (P<0.0001). Similarly, USP18 expression level in the control group was also significantly higher compared to the active (P= 0.0228) and inactive chronic patients (P=0. 0226).

          Conclusion:

          The results of this study showed that the expression level of ISG15 and USP18 but not IL28B were higher in healthy individuals than in those infected with HBV. This difference expression may highlight the role of ISG15 and USP18 in the immune-related mechanism of HBV infection.

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          Most cited references32

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          IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy.

          Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.
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            Immune responses and immunopathology in acute and chronic viral hepatitis.

            Hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for most cases of viral hepatitis. Infection by each type of virus results in a different typical natural disease course and clinical outcome that are determined by virological and immunological factors. HCV tends to establish a chronic persistent infection, whereas HAV does not. HBV is effectively controlled in adults, although it persists for a lifetime after neonatal infection. In this Review, we discuss the similarities and differences in immune responses to and immunopathogenesis of HAV, HBV and HCV infections, which may explain the distinct courses and outcomes of each hepatitis virus infection.
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              Hydrodynamic injection of viral DNA: a mouse model of acute hepatitis B virus infection.

              Hepatitis B virus (HBV) is a prototype for liver-specific pathogens in which the failure of the immune system to mount an effective response leads to chronic infection. Our understanding of the immune response to HBV is incomplete, largely due to the narrow host restriction of this pathogen and the limitations of existing experimental models. We have developed a murine model for studying human HBV replication, immunogenicity, and control. After transfection of hepatocytes in vivo with a replication-competent, over-length, linear HBV genome, viral antigens and replicative intermediates were synthesized and virus was secreted into the blood. Viral antigens disappeared from the blood as early as 7 days after transfection, coincident with the appearance of antiviral antibodies. HBV transcripts and replicative intermediates disappeared from the liver by day 15, after the appearance of antiviral CD8 + T cells. In contrast, the virus persisted for at least 81 days after transfection of NOD/Scid mice, which lack functional T cells, B cells, and natural killer (NK) cells. Thus, the outcome of hydrodynamic transfection of HBV depends on the host immune response, as it is during a natural infection. The methods we describe will allow the examination of viral dynamics in a tightly controlled in vivo system, the application of mutagenesis methods to the study of the HBV life cycle in vivo, and the dissection of the immune response to HBV using genetically modified mice whose immunoregulatory and immune effector functions have been deleted or overexpressed. In addition, this methodology represents a prototype for the study of other known and to-be-discovered liver-specific pathogens.
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                Author and article information

                Journal
                Gastroenterol Hepatol Bed Bench
                Gastroenterol Hepatol Bed Bench
                GHFBB
                Gastroenterology and Hepatology From Bed to Bench
                Shaheed Beheshti University of Medical Sciences (Tehran, Iran )
                2008-2258
                2008-4234
                Winter 2019
                : 12
                : 1
                : 38-45
                Affiliations
                [1 ] Department of Bacteriology and Virology, Shiraz University of Medical Sciences, Shiraz, Iran
                [2 ] Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
                [3 ] Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran
                Author notes
                Reprint or Correspondence: Seyed Younes Hosseini, PhD. Bacteriology and Virology Department, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran. E-mail: Hoseini.younes@gmail.com, ORCID ID: 0000-0002-6407-4004
                Article
                GHFBB-12-1
                6441482
                30949318
                9cf3e104-6d5f-4ac1-a796-736a17c8be04
                ©2019 RIGLD, Research Institute for Gastroenterology and Liver Diseases

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 September 2018
                : 18 December 2018
                Categories
                Original Article

                hepatitis b viruses,immunity,isg15 protein,ifn-lambda-3 protein,usp18

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