• Title/Summary/Keyword: Hepatitis B virus infection

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Hepatitis C Virus Non-structural Protein NS4B Can Modulate an Unfolded Protein Response

  • Zheng Yi;Gao Bo;Ye Li;Kong Lingbao;Jing Wei;Yang Xiaojun;Wu Zhenghui;Ye Linbai
    • 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.

Hepatitis E Virus Methyltransferase Inhibits Type I Interferon Induction by Targeting RIG-I

  • Kang, Sangmin;Choi, Changsun;Choi, Insoo;Han, Kwi-Nam;Roh, Seong Woon;Choi, Jongsun;Kwon, Joseph;Park, Mi-Kyung;Kim, Seong-Jun;Myoung, Jinjong
    • Journal of Microbiology and Biotechnology
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    • v.28 no.9
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    • pp.1554-1562
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    • 2018
  • The type I interferons (IFNs) play a vital role in activation of innate immunity in response to viral infection. Accordingly, viruses have evolved to employ various survival strategies to evade innate immune responses induced by type I IFNs. For example, hepatitis E virus (HEV) encoded papain-like cysteine protease (PCP) has been shown to inhibit IFN activation signaling by suppressing K63-linked de-ubiquitination of retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1), thus effectively inhibiting down-stream activation of IFN signaling. In the present study, we demonstrated that HEV inhibits polyinosinic-polycytidylic acid (poly(I:C))-induced $IFN-{\beta}$ transcriptional induction. Moreover, by using reporter assay with individual HEV-encoded gene, we showed that HEV methyltransferase (MeT), a non-structural protein, significantly decreases RIG-I-induced $IFN-{\beta}$ induction and $NF-{\kappa}B$ signaling activities in a dose-dependent manner. Taken together, we report here that MeT, along with PCP, is responsible for the inhibition of RIG-I-induced activation of type I IFNs, expanding the list of HEV-encoded antagonists of the host innate immunity.

Familial Clustering and Its Associated Factors in Carriers of Hepatitis B Surface Antigen (B형 간염의 가족집적성과 전파경로에 관한 연구)

  • Rhee, Jung-Ae;Lee, Myung-Hak
    • Journal of agricultural medicine and community health
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    • v.17 no.2
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    • pp.129-136
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    • 1992
  • To evaluate the possible route of intrafamilial transmission among carriers of hepatitis B surface antigen ($HB_sAg$), epidemiologic and serologic data were obtained on 107 household contacts of 35 carriers of HBsAg and on 71 household contacts of 25 controls who were negative for serologic markers of hepatitis B virus. The HBsAg prevalence was 26.5% among the contacts of carriers compared to 0.0% among the contacts of controls. And the combined prevalence for all hepatitis markers was 48.5% among the contacts of carriers compared to 26.0% among the contacts of controls(p<0.05). Especially the offspring of carriers showed significantly higher risk in the combined prevalence for all hepatitis markers (p<0.05). There were no significant relationship between HBV infection and past history like acupuncture, transfusion, operation and tattooed. Factors associated with the risk of intrafamilial transmission of HBV were not found in the sharing of household articles such as razor, towel, drinking glass, nail clippers, toothbrush and tableware.

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Inhibition of the Replication of Hepatitis C Virus Replicon with Nuclease-Resistant RNA Aptamers

  • Shin, Kyung-Sook;Lim, Jong-Hoon;Kim, Jung-Hye;Myung, Hee-Joon;Lee, Seong-Wook
    • 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.

Hepatitis B virus X protein promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells by regulating SOCS1

  • Kang, Inho;Kim, Ji Ae;Kim, Jinchul;Lee, Ju Hyeon;Kim, Mi-jee;Ahn, Jeong Keun
    • BMB Reports
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    • v.55 no.5
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    • pp.220-225
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    • 2022
  • Hepatocellular carcinoma (HCC), a primary type of liver cancer, is one of the leading causes of cancer related deaths worldwide. HCC patients have poor prognosis due to intrahepatic and extrahepatic metastasis. Hepatitis B virus (HBV) infection is one of the major causes of various liver diseases including HCC. Among HBV gene products, HBV X protein (HBx) plays an important role in the development and metastasis of HCC. However, the mechanism of HCC metastasis induced by HBx has not been elucidated yet. In this study, for the first time, we report that HBx interacts with the suppressor of cytokine signaling 1 (SOCS1) which negatively controls NF-κB by degrading p65, a subunit of NF-κB. NF-κB activates the transcription of factors associated with epithelial-mesenchymal transition (EMT), a crucial cellular process associated with invasiveness and migration of cancer cells. Here, we report that HBx physically binds to SOCS1, subsequently prevents the ubiquitination of p65, activates the transcription of EMT transcription factors and enhance cell migration and invasiveness, suggesting a new mechanism of HBV-associated HCC metastasis.

Distribution of Sexually Transmitted Viral Diseases in Busan (부산지역 바이러스성 성병 감염양상 연구)

  • Cho, Kyung-Soon;Na, Young-Ran;Joe, Hyeon-Cheol;Lee, Jung-Hee;Jung, Myung-Ju
    • Korean Journal of Microbiology
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    • v.42 no.3
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    • pp.177-184
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    • 2006
  • This study was performed to evaluate the prevalence of high risk Human papilloma virus (HPV), Herpes simplex virus type 1, 2 (HSV-1,2), Hepatitis B virus (HBV) and Human Immuno deficiency virus (HIV) infection with sexual transmitted viral diseases in Busan during 2004 to 2005. six hundred seventy four samples of cervical swabs were tested for sexually transmitted viral diseases. Among the isolated viruses, 23 (3.4%) samples were HPV and 3 (0.4%) and 9 (1.3%) samples were HSV 1 and 2, respectively. Among the 586 serum samples tested for viruses, HSV IgM 121 (3.6%), HSV-1 IgG 487 (83.1%), HSV-2 IgG 135 (23.0%), HBsAg 26 (4.4%), HBeAg 7 (1.2%), and HIV (0%) types were found. HPV genotypes were detected in 16 patients, of which 13 cases were high risk type HPV, 3 cases were low risk type HPV, and multi infection were detected in 7 cases. In the age distribution of the patients, 7.2% of infection tested from cervical swabs occurred in under the age of 20, while 100% of infection was found to occur in those who were 40 years old or older in the serum samples. The outbreak pattern in their occupations was found to be the highest at the health organization (amusement quarter) for the cervical swabs, and at infirmary (commercial sex worker) for the serum samples, respectively.

Expression of Phospholipase A2 Receptor in Pediatric Hepatitis B Virus-Related Membranous Nephropathy

  • Choi, Sung-Eun;Bae, Yoon Sung;Lee, Keum Hwa;Shin, Jae Il;Jeong, Hyeon Joo;Lim, Beom Jin
    • Childhood Kidney Diseases
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    • v.24 no.1
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    • pp.36-41
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    • 2020
  • Purpose: Hepatitis B virus (HBV) infection is among etiologies of secondary membranous nephropathy (MN) in pediatric patients. We evaluated expression of phospholipase A2 receptor (PLA2R), a specific target antigen of primary MN, in pediatric HBV-related MN. Methods: We retrospectively reviewed patients with biopsy-proven HBV-related MN from the renal biopsy registry and electronic medical records of Severance Hospital, Seoul, Korea, from 1993 to 2004. Paraffin-embedded human kidney tissues were retrieved and immunohistochemically stained for PLA2R. Results: Ten pediatric patients with 13 biopsied specimens were reviewed. The predominant pathological stage was stage II-III, and second was stage II. The intensity of staining for IgG was greatest, with less intense staining for IgM, IgA, C3, C4, and C1q. All the patients had angiotensin-converting enzyme inhibitor combined with glucocorticoid, and four patients converted to cyclosporine treatment from glucocorticoid monotherapy. Urinalysis of all the patients normalized after variable period. PLA2R staining was demonstrated in the outer glomerulus in 3 out of 13 biopsies, 2 of which were obtained from the same patient over a 5-year interval. Conclusions: PLA2R was expressed in a small number of cases diagnosed as pediatric HBV-related MN, indicating that some HBV-related MN cases may be primary MN concurrent with HBV infection.

Independent and Additive Interaction Between Tumor Necrosis Factor β +252 Polymorphisms and Chronic Hepatitis B and C Virus Infection on Risk and Prognosis of Hepatocellular Carcinoma: a Case-Control Study

  • Jeng, Jen-Eing;Wu, Hui-Fang;Tsai, Meng-Feng;Tsai, Huey-Ru;Chuang, Lea-Yea;Lin, Zu-Yau;Hsieh, Min-Yuh;Chen, Shinn-Chern;Chuang, Wan-Lung;Wang, Liang-Yen;Yu, Ming-Lung;Dai, Chia-Yen;Tsai, Jung-Fa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10209-10215
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    • 2015
  • To assess the contribution of tumor necrosis factor $(TNF){\beta}$ +252 polymorphisms to risk and prognosis of hepatocellular carcinoma (HCC), we enrolled 150 pairs of sex- and age-matched patients with HCC, patients with cirrhosis alone, and unrelated healthy controls. $TNF{\beta}$ +252 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism. Multivariate analysis indicated that $TNF{\beta}$ G/G genotype [odds ratio (OR), 3.64; 95%CI, 1.49-8.91], hepatitis B surface antigen (OR, 16.38; 95%CI, 8.30-32.33), and antibodies to hepatitis C virus (HCV) (OR, 39.11; 95%CI, 14.83-103.14) were independent risk factors for HCC. There was an additive interaction between $TNF{\beta}$ G/G genotype and chronic hepatitis B virus (HBV)/HCV infection (synergy index=1.15). Multivariate analysis indicated that factors associated with $TNF{\beta}$ G/G genotype included cirrhosis with Child-Pugh C (OR, 4.06; 95%CI, 1.34-12.29), thrombocytopenia (OR, 6.55; 95%CI, 1.46-29.43), and higher serum ${\alpha}$-fetoprotein concentration (OR, 2.53; 95%CI, 1.14-5.62). Patients with $TNF{\beta}$ G/G genotype had poor cumulative survival (p=0.005). Cox proportional hazard model indicated that $TNF{\beta}$ G/G genotype was a biomarker for poor HCC survival (hazard ratio, 1.70; 95%CI, 1.07-2.69). In conclusion, there are independent and additive effects between $TNF{\beta}$ G/G genotype and chronic HBV/HCV infection on risk for HCC. It is a biomarker for poor HCC survival. Carriage of this genotype correlates with disease severity and advanced hepatic fibrosis, which may contribute to a higher risk and poor survival of HCC. Chronic HBV/HCV infected subjects with this genotype should receive more intensive surveillance for early detection of HCC.

Simultaneous Infection of Duck Hepatitis Virus and Salmonella typhimurium in Ducklings (오리에서 Duck Hepatitis Virus와 Salmonella typhimurium의 혼합 감염 증례)

  • Lee, Hae-Rim;Koo, Bon-Sang;Lee, Young-Ju;Mo, In-Pil
    • Korean Journal of Poultry Science
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    • v.38 no.1
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    • pp.13-19
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    • 2011
  • In January 2010, high mortalities of ducklings occurred in two adjacent farms. Ducklings in farm A showed neurologic signs including paddling, opisthotonus and lameness, but ducklings from farm B had no specific clinical signs. At post mortem, diffused hemorrhagic spots in the liver and hemorrhages in the small intestine were observed in ducklings from farm A, and ducklings from farm B had only proventricular ulceration. Microscopically, multiple necrosis of hepatocytes, hyperplasia of the bile ducts, hemorrhages, infiltration of lymphocytes and bacterial colonies were commonly observed in the liver of ducklings from both farms. Also, type A and C duck hepatitis virus (DHV) were isolated from farm A and farm B, respectively and Salmonella typhimurium was commonly isolated and identified serologically and biochemically. To our knowledge, this is the first report about the co-infection of DHV and Salmonella typhimurium in ducklings, and co-circulation of type A and C duck hepatitis viruses in Korea.

A study on Hepatitis B and knowledge about AIDS of dental hygiene student in Korea (전국 치위생과 학생들의 B형간염과 AIDS에 관한 지식도 조사)

  • Song, Kyung-Hee;Bae, Bong-Jin
    • Journal of Korean society of Dental Hygiene
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    • v.1 no.2
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    • pp.181-192
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    • 2001
  • The purpose of this was to evaluate the level of knowledge about Hepatitis B and AIDS among dental hygiene students at six dental hygiene educational programs in nationwide, compare the findings to those of Song's study. 1703 dental hygiene students surveyed by mail and answered a questionnaire, using the questionnaire used developed by DiClemente el al., on Hepatitis B vaccination, antibody production, experience of unintentional needle stick injuries, experience of surgical operation and blood transfusion, personal risk factors for HBV and HIV, management of HBV and HIV postexposure management et al. The data indicated that dental hygiene students (79.0%) in this study had more HIV vaccination than dental hygiene(74.3%) in Song's study. As for recognition of antibody production after Hepatitis B vaccination, only 34.6% of respondents answered they knew having antibody production and 95% of respondents knew not having antibody production. Over one-half of the respondents (55%) answered they didn't even recognize having antibody production. 52.3 percent of dental hygiene students experienced unintentional needle stick injuries. The findings on the knowledge about Hepatitis B and AIDS were that dental hygienists (76.5 points) received higher mean score than those of dental hygiene students (71.0 points) and that the distribution of right answer rate also showed wider range in dental hygiene students (27.7~97.5%) than those of dental hygienist (41.2~99.5%). There were no statistical differences among dental hygiene education programs. Finding of this study support that the curriculum of dental hygiene program should include instruction on sources and methods of transmission of infectious diseases, risk of virus transmission in the workplace and principles of infection control. Furthermore, infection-control practices should be utilized routinely and their application to dental personnel, management of HBV and HIV postexposure management. Furthermore, for preventing the further spread of infectious diseases (HBV, HIV and AIDS${\cdots}$) caused by bloodborne viruses, imposing an obligation rather than recommendation on Hepatitis B vaccination to all dental personnel and routinely utilizing infection-control guidelines for all dental patients in dental practices (include dental educational programs) should be accomplished by coordination the government agency.

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