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https://www.readbyqxmd.com/read/28425405/cost-effectiveness-and-clinical-impact-of-antiviral-strategies-of-hbeag-positive-and-negative-chronic-hepatitis-b
#1
Itziar Oyagüez, María Buti, Max Brosa, Magdalena Rueda, Miguel A Casado
INTRODUCTION: Chronic hepatitis B (CHB) is associated with high burden and healthcare costs. Virologic response achieved with antivirals is associated with progression avoidance. This study aimed to estimate the efficiency and clinical impact of antiviral strategies in CHB patients. MATERIAL AND METHODS: A Markov model estimated lifetime complications and direct costs in both, HBeAg-positive and HBeAg-negative cohorts. Strategy 1 (71% of treated population) and strategy 2 (100%), both based on pegylated interferon (peg-IFN) followed by oral tenofovir or entecavir, were compared to no treatment...
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28407271/a-potent-hbsag-response-in-subjects-with-inactive-hbsag-carrier-treated-with-pegylated-interferon-alpha
#2
Zhenhuan Cao, Yali Liu, Lina Ma, Junfeng Lu, Yi Jin, Shan Ren, Zhimin He, Chengli Shen, Xinyue Chen
BACKGROUND: HBsAg clearance represents a clinical cure although the clearance rate is extremely low. The aim of this study was to evaluate the feasibility and safety profiles of pegylated-interferon α-2a (PEG-IFNα-2a) as a therapeutic option for inactive HBsAg carriers (IHCs). METHODS: 144 IHCs were enrolled and divided into a therapeutic group (102 subjects) and control group (42 subjects). PEG-IFNα-2a and PEG-IFNα-2a combined with Adefovir Dipivoxil (ADV) were used for treatment group subjects with hepatitis B virus (HBV) DNA <20 IU/mL and 20 IU/mL≤HBV DNA<2000 IU/mL, respectively...
April 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28402024/marburg-virus-like-particles-produced-in-insect-cells-induce-neutralizing-antibodies-in-rhesus-macaques
#3
Weiwei Gai, Xuexing Zheng, Chong Wang, Yongkun Zhao, Qi Wang, Hualei Wang, Gary Wong, Ying Xie, Haijun Wang, Zengguo Cao, Na Feng, Hang Chi, Tiecheng Wang, Yuwei Gao, Junjie Shan, Songtao Yang, Xianzhu Xia
Marburg virus (MARV), which is one of the most virulent agents in the world, causes lethal haemorrhagic fever in humans and nonhuman primates (NHPs) with a mortality rate of up to 90%. Currently, there is no effective treatment or approved vaccine for MARV for human use to control disease outbreak and spread. Virus-like particles (VLPs), which are morphologically identical to the native infectious virus particle, are efficacious as vaccines against many viruses, including human papilloma virus (HPV), porcine circovirus (PCV) type 2 and hepatitis B virus (HBV)...
April 12, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28399146/interferon-inducible-ribonuclease-isg20-inhibits-hepatitis-b-virus-replication-through-directly-binding-to-the-epsilon-stem-loop-structure-of-viral-rna
#4
Yuanjie Liu, Hui Nie, Richeng Mao, Bidisha Mitra, Dawei Cai, Ran Yan, Ju-Tao Guo, Timothy M Block, Nadir Mechti, Haitao Guo
Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription of a viral RNA pregenome. We report herein that the interferon (IFN) stimulated exoribonuclease gene of 20 KD (ISG20) inhibits HBV replication through degradation of HBV RNA. ISG20 expression was observed at basal level and was highly upregulated upon IFN treatment in hepatocytes, and knock down of ISG20 resulted in elevation of HBV replication and attenuation of IFN-mediated antiviral effect. The sequence element conferring the susceptibility of HBV RNA to ISG20-mediated RNA degradation was mapped at the HBV RNA terminal redundant region containing epsilon (ε) stem-loop...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28392573/inducible-rubicon-facilitates-viral-replication-by-antagonizing-interferon-production
#5
Yushun Wan, Wei Cao, Tao Han, Sheng Ren, Jian Feng, TieLong Chen, Jun Wang, Ruth Broering, Mengji Lu, Ying Zhu
The RUN domain Beclin-1-interacting cysteine-rich-containing (Rubicon) protein is involved in the maturation step of autophagy and the endocytic pathway as a Beclin-1-binding partner, but little is known regarding the role of Rubicon during viral infection. Here, we performed functional studies of the identified target in interferon (IFN) signaling pathways associated with Rubicon to elucidate the mechanisms of viral resistance to IFN. The Rubicon protein levels were elevated in peripheral blood mononuclear cells, sera and liver tissues from patients with hepatitis B virus (HBV) infection relative to those in healthy individuals...
April 10, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28383274/past-current-and-future-developments-of-therapeutic-agents-for-treatment-of-chronic-hepatitis-b-virus-infection
#6
Yameng Pei, Chunting Wang, S Frank Yan, Gang Liu
For decades, treatment of hepatitis B virus (HBV) infection has been relying on interferon (IFN)-based therapies and nucleoside/nucleotide analogues (NAs) that selectively target the viral polymerase reverse transcriptase (RT) domain and thereby disrupt HBV viral DNA synthesis. We have summarized here the key steps in the HBV viral life cycle, which could potentially be targeted by novel anti-HBV therapeutics. A wide range of next-generation direct antiviral agents (DAAs) with distinct mechanisms of actions are discussed, including entry inhibitors, transcription inhibitors, nucleoside/nucleotide analogues, inhibitors of viral ribonuclease H (RNase H), modulators of viral capsid assembly, inhibitors of HBV surface antigen (HBsAg) secretion, RNA interference (RNAi) gene silencers, antisense oligonucleotides (ASOs), and natural products...
April 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28381384/novel-hbv-mutations-and-their-value-in-predicting-efficacy-of-conventional-interferon
#7
Da-Xian Wu, Xiao-Yu Fu, Guo-Zhong Gong, Ke-Wei Sun, Huan-Yu Gong, Ling Wang, Juan Wu, De-Ming Tan
BACKGROUND: Accumulating studies assessing the impacts of hot spot mutations on conventional interferon (IFN) efficacy come to discrepant conclusions; studies regarding the mutations in S and RT regions are also unclear. The present study aimed to evaluate the impacts of HBV mutations on the efficacy of conventional IFN. METHODS: A total of 126 patients who received conventional IFN treatment for 48 weeks were enrolled. Biochemical and serological parameters were routinely tested...
April 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28369997/gene-expression-profile-after-knockdown-of-usp18-in-hepg2-2-15-cells
#8
Lin Li, Qing-Song Lei, Ling-Na Kong, Shu-Jun Zhang, Bo Qin
In our previous work, we found that the expression of ubiquitin-specific protease 18 (USP18), also known as UBP43, is associated with the efficiency of interferon alpha (IFN-α) treatment in patients with chronic hepatitis B (CHB). To elucidate the influence of USP18 on hepatitis B virus (HBV) replication and the mechanism of this activity, we silenced USP18 by introducing short hairpin RNA (shRNA) into Hepg2.2.15 cells. To identify the changed genes and pathways in Hepg2.2.15-shRNA-USP18 cells, we performed a microarray gene expression analysis to compare the Hepg2...
March 31, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28367455/secreted-interferon-inducible-factors-restrict-hepatitis-b-and-c-virus-entry-in-vitro
#9
Yuchen Xia, Xiaoming Cheng, Christoph K Blossey, Karin Wisskirchen, Knud Esser, Ulrike Protzer
Interferon-α (IFN-α) has been used for more than 20 years as the first-line therapy for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, because it has a number of antiviral effects. In this study, we describe a novel mode of its antiviral action. We demonstrate that the supernatant from IFN-α-treated cultured cells restricted HBV and HCV infection by inhibiting viral entry into hepatoma cells. The factors contained in the supernatant competed with the virus for binding to heparan glycosaminoglycans-the nonspecific attachment step shared by HBV and HCV...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28363866/interferon-induces-interleukin-8-and-bone-marrow-stromal-cell-antigen-2-expression-inhibiting-the-production-of-hepatitis-b-virus-surface-antigen-from-human-hepatocytes
#10
Yuki Haga, Tatsuo Kanda, Shingo Nakamoto, Masato Nakamura, Reina Sasaki, Shuang Wu, Osamu Yokosuka
Hepatitis B virus (HBV) surface antigen (HBsAg) loss is one of the treatment goals of chronic HBV infection. Bone marrow stromal cell antigen 2 (BST2) is one of the interferon (IFN)-stimulated genes (ISGs) and inhibits the release of various enveloped viruses. Here we examined the effects of antiviral treatment on HBsAg levels and its intracellular mechanism in HBsAg-producing hepatocytes. In PLC/PRF/5 and Huh1, IFNα-2a treatment decreased HBsAg levels in their conditioned media. Upregulation of interleukin 8 (IL8), toll-like receptor 2 (TLR2) and interferon gamma-induced protein 10 (IP10) mRNAs was associated with the reduction of HBsAg in both PLC/PRF/5 and Huh1...
May 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342861/microrna-548j-inhibits-type-i-interferon-production-by-targeting-zbtb11-in-patients-with-chronic-hepatitis-b
#11
Kangkang Yu, Qian Li, Qi Cheng, Chong Huang, Jianming Zheng, Shengsen Chen, Qingxia Ling, Mengqi Zhu, Mingquan Chen, Guangfeng Shi, Ning Li
Type I IFNs play crucial roles in antiviral immune responses. By inducing cellular resistance to viral infection and apoptosis of virus-infected cells, they impair virus replication and eliminate the invading pathogens. However, in CHB patients, generation of type I IFN was significantly impaired and the underlying mechanisms have not been fully understood. MicroRNA-548 family has been implicated in regulating antiviral response upon various infections. Here we explored the potential role of miR-548j in modulating type I IFN production in CHB...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28341749/suppression-of-interferon-mediated-anti-hbv-response-by-single-cpg-methylation-in-the-5-utr-of-trim22
#12
Keo-Heun Lim, Eun-Sook Park, Doo Hyun Kim, Kyung Cho Cho, Kwang Pyo Kim, Yong Kwang Park, Sung Hyun Ahn, Seung Hwa Park, Kee-Hwan Kim, Chang Wook Kim, Hong Seok Kang, Ah Ram Lee, Soree Park, Heewoo Sim, Juhee Won, Kieun Seok, Jueng Soo You, Jeong-Hoon Lee, Nam-Joon Yi, Kwang-Woong Lee, Kyung-Suk Suh, Baik L Seong, Kyun-Hwan Kim
OBJECTIVE: Interferons (IFNs) mediate direct antiviral activity. They play a crucial role in the early host immune response against viral infections. However, IFN therapy for HBV infection is less effective than for other viral infections. DESIGN: We explored the cellular targets of HBV in response to IFNs using proteome-wide screening. RESULTS: Using LC-MS/MS, we identified proteins downregulated and upregulated by IFN treatment in HBV X protein (HBx)-stable and control cells...
March 23, 2017: Gut
https://www.readbyqxmd.com/read/28331562/polymorphism-of-ifn-%C3%AE-874-t-a-in-syrian-patients-with-chronic-hepatitis-b
#13
Mohamad Al Kadi, Fawza Monem
AIM: This study aimed to investigate the association of IFN- γ +874 (T/A) polymorphism with susceptibility to chronic HBV infection in the Syrian population. BACKGROUND: Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. Therefore, polymorphisms in genes encoding the cytokines, which are responsible for regulation of the immune response, can affect the course and outcome of the infection. The IFN-γ +874 T/A polymorphism affects the expression of IFN-γ, which has been shown to be crucial to HBV clearance...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28331190/natural-killer-cell-activation-contributes-to-hepatitis-b-viral-control-in-a-mouse-model
#14
Shiwen Tong, Guangze Liu, Minghong Li, Xiumei Li, Qian Liu, Hong Peng, Shiying Li, Hong Ren, Wenwei Yin
The roles of CD4 + T cells and CD8 + T cells in hepatitis B virus (HBV) infection have been well documented. However, the role of innate immunity in HBV infection remains obscure. Here we examined the effect of activation of innate immunity by polyinosinic: polycytidylic acid (PolyI:C) on HBV infection. A chronic HBV replication mouse model was established by hydrodynamical injection of pAAV/HBV1.2 plasmid into C57BL/6 mice. We found that HBV did not seem to induce an active NK-cell response in the mouse model...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28328926/frequency-and-role-of-nkp46-and-nkg2a-in-hepatitis-b-virus-infection
#15
Teppei Yoshioka, Tomohide Tatsumi, Takuya Miyagi, Kaori Mukai, Kumiko Nishio, Akira Nishio, Yoshinobu Yokoyama, Takahiro Suda, Tadashi Kegasawa, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Tetsuo Takehara
BACKGROUND AND AIM: Natural Killer (NK) cells are involved in the control of viral infection. However, the role of NK cells in chronic hepatitis B (CHB) remains unclear. This study investigated the frequencies and roles of NK cells in CHB, with a focus on activating receptor NKp46 and inhibitory receptor NKG2A. PATIENTS/METHOD: Peripheral blood lymphocytes were obtained from 71 CHB patients and 37 healthy subjects (HS). The expressions of NKp46 and NKG2A were analyzed using flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28297795/-the-potential-use-of-serum-hbv-rna-to-guide-the-functional-cure-of-chronic-hepatitis-b
#16
F M Lu, J Wang, X M Chen, J N Jiang, W H Zhang, J M Zhao, H Ren, J L Hou, N S Xia
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in infected hepatocytes is the main cause of off-therapy viral rebound. The half-life of cccDNA is only 33-50 days, so the conversion of newly synthesized rcDNA to cccDNA in the nucleus is essential for the maintenance of cccDNA pool in infected hepatocytes. Though not directly targeting the existing cccDNA, current nucleos(t)ide analogues (NAs) may exhaust the cccDNA reservoir by blocking the rcDNA formation. Indeed, a prolonged consolidation therapy post loss of serum HBV DNA can achieve sustained remission and thus safe drug discontinuation in a small proportion of chronic hepatitis B (CHB) patients...
February 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28291736/association-of-vitamin-d-related-genetic-variations-and-treatment-response-to-pegylated-interferon-in-patients-with-chronic-hepatitis-b
#17
Umaporn Limothai, Natthaya Chuaypen, Apichaya Khlaiphuengsin, Salyavit Chittmittraprap, Yong Poovorawan, Pisit Tangkijvanich
BACKGROUND: Vitamin D, a potent immune-modulator, has been linked to the pathogenesis of chronic hepatitis B (CHB). This study was aimed at investigating the association between single nucleotide polymorphisms (SNPs) in vitamin D-related genes and treatment response to pegylated interferon (PEG-IFN) in patients with CHB. METHODS: A total 275 Thai patients (122 HBeAg-positive and 153 HBeAg-negative CHB) treated with 48-week PEG-IFN were recruited. Virological response (VR) at 48 weeks post treatment was defined as HBeAg seroconversion plus HBV DNA <2,000 IU/mL for HBeAg-positive CHB and HBV DNA <2,000 IU/mL for HBeAg-negative CHB...
March 14, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28291251/activated-hepatic-stellate-cells-impair-nk-cell-anti-fibrosis-capacity-through-a-tgf-%C3%AE-dependent-emperipolesis-in-hbv-cirrhotic-patients
#18
Jijing Shi, Juanjuan Zhao, Xin Zhang, Yongqian Cheng, Jinhua Hu, Yuanyuan Li, Xin Zhao, Qinghua Shang, Yanling Sun, Bo Tu, Lei Shi, Bin Gao, Fu-Sheng Wang, Zheng Zhang
Natural killer (NK) cells can induce liver fibrosis remission by killing hepatic stellate cells (HSCs) and producing interferon (IFN)-γ in a mouse model; however, their anti-fibrotic immune-characteristics and regulatory mechanisms by HSCs remain to be determined, especially in livers from HBV-infected liver cirrhosis (LC) patients. We analyzed frequency, phenotype and anti-fibrotic function of hepatic and peripheral NK subsets in 43 HBV-LC patients. We found that hepatic NK subsets from LC patients displayed a decreased frequency, activation status and anti-fibrotic activity compared with those from chronic hepatitis B patients, which were mainly mediated by increased intrahepatic tumour-growth factor (TGF)-β because blockade of TGF-β significantly reversed NK anti-fibrotic function in vitro...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274240/effect-of-48-week-pegylated-interferon-%C3%AE-2a-or-nucleos-t-ide-analogue-therapy-on-renal-function-in-chinese-patients-with-chronic-hepatitis-b
#19
Ye Zhang, Wei-Lu Zhang, Xiao-Wen Pang, Lin-Xu Wang, Xin Wei, Chang-Xing Huang, Xue-Fan Bai, Shuai Han, Lin-Na Liu, Jian-Qi Lian
BACKGROUND: Controversy remains as to whether antiviral agents contribute to renal dysfunction in patients with chronic hepatitis B virus (HBV) infection. Thus, the aim of study was to analyze the changes in renal function of chronic hepatitis B (CHB) patients in response to anti-HBV therapy and the association with treatments. METHOD: We performed a retrospective observational cohort study to investigate factors associated with renal function in 249 Chinese CHB patients who were treated with pegylated interferon α-2a (PEG-IFN-α-2a) or nucleos(t)ide analogues for 48 weeks...
March 9, 2017: Virology Journal
https://www.readbyqxmd.com/read/28273905/nkg2d-modulates-aggravation-of-liver-inflammation-by-activating-nk-cells-in-hbv-infection
#20
Yadong Wang, Wei Wang, Chuan Shen, Yong Wang, Mingjing Jiao, Weiyan Yu, Hongzhu Yin, Xiaobo Shang, Qianfei Liang, Caiyan Zhao
Hepatitis B virus (HBV) infection is thought to be an immune-mediated liver disease. The mechanisms underlying natural killer (NK) cell group 2D receptor (NKG2D) that activates NK cells and participates in anti-HBV immunity and immunopathology has not been thoroughly elucidated. Peripheral NKG2D(+) and IFN-γ(+) NK cells frequencies and intrahepatic NKG2D and IFN-γ mRNA and protein expressions were determined in HBV-infected patients. Levels of NKG2D and IFN-γ mRNA and protein in NK cells, co-cultured with HBV-replicating HepG2 cells with or without NKG2D blockade, were analyzed...
December 2017: Scientific Reports
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