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HBV IFN

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https://www.readbyqxmd.com/read/28527664/a-new-hdv-mouse-model-identifies-mitochondrial-antiviral-signaling-protein-mavs-as-a-key-player-in-ifn-%C3%AE-induction
#1
Lester Suárez-Amarán, Carla Usai, Marianna Di Scala, Cristina Godoy, Yi Ni, Mirja Hommel, Laura Palomo, Víctor Segura, Cristina Olagüe, Africa Vales, Alicia Ruiz-Ripa, Maria Buti, Eduardo Salido, Jesús Prieto, Stephan Urban, Francisco Rodríguez-Frias, Rafael Aldabe, Gloria González-Aseguinolaza
BACKGROUND & AIMS: Studying hepatitis delta virus (HDV) and developing new treatments is hampered by the limited availability of small animal models. Here a description of a robust mouse model of HDV infection that mimics several important characteristics of the human disease is presented. METHODS: HDV- and HBV-replication competent genomes were delivered to the mouse liver using adeno-associated viruses (AAV) (AAV-HDV and AAV-HBV). Viral load, antigen expression and genomes were quantified at different time points after AAV injection...
May 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28496097/hepatitis-b-virus-e-antigen-activates-the-suppressor-of-cytokine-signaling-2-to-repress-interferon-action
#2
Yi Yu, Pin Wan, Yanhua Cao, Wei Zhang, Junbo Chen, Li Tan, Yan Wang, Zhichen Sun, Qi Zhang, Yushun Wan, Ying Zhu, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu
Hepatitis B virus (HBV) infection causes acute hepatitis B (AHB), chronic hepatitis B (CHB), liver cirrhosis (LC), and eventually hepatocellular carcinoma (HCC). The presence of hepatitis B e antigen (HBeAg) in the serum generally indicates ongoing viral replication and disease progression. However, the mechanism by which HBeAg regulates HBV infection remains unclear. Interferons (IFNs) are pleiotropic cytokines that participate in host innate immunity. After binding to receptors, IFNs activate the JAK/STAT pathway to stimulate expression of IFN-stimulated genes (ISGs), leading to induction of antiviral responses...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28487055/recombinant-vaccinia-vector-based-vaccine-tiantan-boosting-a-novel-hbv-subunit-vaccine-induced-more-robust-and-lasting-immunity-in-rhesus-macaques
#3
Yao Deng, Xia Chuai, Pan Chen, Hong Chen, Wen Wang, Li Ruan, Wenhui Li, Wenjie Tan
This study explored several prime-boost strategies in rhesus macaques using various novel hepatitis B virus (HBV) vaccines that showed promise as prophylactic and therapeutic approaches in our previous study using in a mouse model. The tested vaccines included an HBV particle subunit (HBSS1) vaccine and the recombinant vaccinia (RVJSS1) or adenoviral (rAdSS1) vector-based vaccines containing S (1-223aa) and PreS1 (21-47aa). The strength and maintenance of humoral activity (IgG and neutralizing antibodies) and cellular immunity (interferon-γ production assessed by IFN-γ enzyme-linked immunosorbent spot (ELISpot) assay) were investigated in a longitudinal study following various vaccination protocols until 79weeks post-vaccination...
June 5, 2017: Vaccine
https://www.readbyqxmd.com/read/28480296/hepatitis-b-virus-reactivation-in-patients-receiving-interferon-free-direct-acting-antiviral-agents-for-chronic-hepatitis-c-virus-infection
#4
Chen-Hua Liu, Chun-Jen Liu, Tung-Hung Su, Yu-Jen Fang, Hung-Chih Yang, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao
BACKGROUND: Little is known about the risk of hepatitis B virus (HBV) reactivation in patients receiving interferon (IFN)-free direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV). METHODS: Patients who were seropositive for HBV core antibody and who received IFN-free DAAs for HCV were enrolled. Hepatitis B virus reactivation was defined as reappearance of serum HBV deoxyribonucleic acid (DNA) ≥100 IU/mL in patients with baseline undetectable viral load, or ≥2 log10 IU/mL increase of HBV DNA in patients with baseline detectable viral load...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28450868/hepatitis-b-virus-immunopathology-model-systems-and-current-therapies
#5
REVIEW
Praneet Sandhu, Mohammad Haque, Tessa Humphries-Bickley, Swetha Ravi, Jianxun Song
Most people develop acute hepatitis B virus (HBV)-related hepatitis that is controlled by both humoral and cellular immune responses following acute infection. However, a number of individuals in HBV-endemic areas fail to resolve the infection and consequently become chronic carriers. While a vaccine is available and new antiviral drugs are being developed, elimination of persistently infected cells is still a major issue. Standard treatment in HBV infection includes IFN-α, nucleoside, or nucleotide analogs, which has direct antiviral activity and immune modulatory capacities...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28445966/interferon-alpha-antagonizes-the-anti-hepatoma-activity-of-the-oncolytic-virus-m1-by-stimulating-anti-viral-immunity
#6
Liu Ying, Hu Cheng, Xu Wen Xiong, Lin Yuan, Zhang Hai Peng, Zhong Wen Wen, Liang Jian Ka, Xiao Xiao, Cai Jing, Tan Ya Qian, Gao Zhi Liang, Yan Guang Mei, Zhu Wen Bo, Peng Liang
Alpha virus M1 is an oncolytic virus that targets zinc-finger antiviral protein (ZAP)-defective cancer cells, and may be useful for treatment of hepatocellular carcinoma (HCC). Most of HCC patients have hepatitis and need long-term antiviral medication. Thus, it is necessary to clarify whether anti-virus medicines influence oncolytic effect of M1. We examined the effect of drugs used to treat hepatitis B/C on M1-mediated oncolysis in vitro and in vivo. Interferon (IFN)-α induces expression of antiviral IFN-stimulated genes (ISGs) in HCC cells with moderate sensitivity to M1 virus...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425405/cost-effectiveness-and-clinical-impact-of-antiviral-strategies-of-hbeag-positive-and-negative-chronic-hepatitis-b
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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