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https://www.readbyqxmd.com/read/28709658/ngago-gdna-system-efficiently-suppresses-hepatitis-b-virus-replication-through-accelerating-decay-of-pregenomic-rna
#1
Zhuanchang Wu, Siyu Tan, Leiqi Xu, Lifen Gao, Haizhen Zhu, Chunhong Ma, Xiaohong Liang
Covalently closed circular DNA (cccDNA) in the hepatocytes nucleus is responsible for persistent infection of Hepatitis B virus (HBV). Current antiviral therapy drugs nucleos(t)ide analogs or interferon fail to eradicate HBV cccDNA. Genome editing technique provides an effective approach for HBV treatment through targeting viral cccDNA. Natronobacterium gregoryi Argonaute (NgAgo)-guide DNA (gDNA) system with powerful genome editing prompts us to explore its application in inhibiting HBV replication. Preliminary function verification indicated that NgAgo/EGFP-gDNA obviously inhibited EGFP expression...
July 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28709006/compartmental-hbv-evolution-and-replication-in-liver-and-extrahepatic-sites-after-nucleos-tide-analogue-therapy-in-chronic-hepatitis-b-carriers
#2
Shan Gao, Zhong-Ping Duan, Yu Chen, Frank van der Meer, Samuel S Lee, Carla Osiowy, Guido van Marle, Carla S Coffin
BACKGROUND: Hepatitis B virus (HBV) variants are associated with nucleos/tide analogue (NA) response and liver disease but it is unknown whether NA influences extrahepatic HBV persistence. OBJECTIVES: To investigate HBV replication and genetic evolution in hepatic and extrahepatic sites of chronic hepatitis B (CHB) before and after NA therapy. STUDY DESIGN: A total of 13 paired plasma, peripheral blood mononuclear cells (PBMC), were collected from chronic HBV carriers at baseline and after a median 53 weeks NA therapy as well as liver biopsy (N=7 baseline, N=5 follow-up)...
July 5, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28703895/hbv-reactivation-in-patients-with-hcv-hbv-cirrhosis-on-treatment-with-direct-acting-antivirals
#3
Vincenza Calvaruso, Donatella Ferraro, Anna Licata, Maria Grazia Bavetta, Salvatore Petta, Fabrizio Bronte, Giuseppina Colomba, Antonio Craxì, Vito Di Marco
Anecdotal reports suggest that patients with chronic HCV hepatitis and overt or occult HBV co-infection may reactivate HBV when HCV is suppressed or cleared by DAAs. We assessed the prevalence of overt or previous HBV co-infection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up...
July 13, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28697919/fatty-acid-translocase-promoted-hepatitis-b-virus-replication-by-upregulating-the-levels-of-hepatic-cytosolic-calcium
#4
Jian Huang, Lei Zhao, Ping Yang, Zhen Chen, Xiong Z Ruan, Ailong Huang, Ni Tang, Yaxi Chen
Hepatitis B virus (HBV) is designated a "metabolovirus" due to the intimate connection between the virus and host metabolism. The nutrition state of the host plays a relevant role in the severity of HBV infection. Metabolic syndrome (MS) is prone to increasing HBV DNA loads and accelerating the progression of liver disease in patients with chronic hepatitis B (CHB). Cluster of differentiation 36 (CD36), also named fatty acid translocase, is known to facilitate long-chain fatty acid uptake and contribute to the development of MS...
July 8, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28694000/boceprevir-based-triple-therapy-to-rescue-hcv-genotype-1-hbv-dually-infected-patients-refractory-to-peginterferon-plus-ribavirin-combination-therapy-in-taiwan
#5
Meng-Hsuan Hsieh, Ming-Lun Yeh, Tung-Hung Su, Ta-Wei Liu, Chuang-Feng Huang, Ching-I Huang, Shu-Chi Wang, Jee-Fu Huang, Chia-Yen Dai, Jia-Horng Kao, Wan-Long Chuang, Pei-Jer Chen, Chun-Jen Liu, Ming-Lung Yu
BACKGROUND/PURPOSE: The role of directly-acting antivirals (DAA)-containing regimens in the treatment of patients dually-infected with hepatitis C virus (HCV) and hepatitis B virus (HBV) remains unclear. The pilot study aimed to explore the safety and efficacy of a protease inhibitor, boceprevir, in combination with peginterferon/ribavirin for HCV genotype 1 (HCV-1)/HBV dually-infected patients refractory to prior peginterferon/ribavirin. METHODS: Twelve peginterferon-experienced patients dually-infected with HCV-1/HBV were assigned to receive boceprevir 800 mg, twice a day, plus peginterferon-α 2b 1...
July 7, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28687901/virological-and-clinical-characteristics-of-hepatitis-b-virus-genotype-a
#6
REVIEW
Kiyoaki Ito, Masashi Yoneda, Kazumasa Sakamoto, Masashi Mizokami
Hepatitis B virus (HBV) infection is one of the most prevalent chronic viral infections in humans. The overall prevalence of hepatitis B surface antigen (HBsAg) is reported to be 3.6%; however, it varies depending upon the geographic area. HBV is classified into ten genotypes (A through J) on the basis of an intergroup genomic divergence of > 8%. Specifically, HBV genotype A exhibits several unique virological and clinical characteristics and can be further classified into seven subtypes. Among them, subtype A2 or Ae (A2/[e]) is occasionally responsible for nosocomial infection and among homosexual males...
July 7, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28678687/ceruloplasmin-inhibits-the-production-of-extracellular-hepatitis-b-virions-by-targeting-its-middle-surface-protein
#7
Kaitao Zhao, Chunchen Wu, Yongxuan Yao, Liang Cao, Zhenhua Zhang, Yifei Yuan, Yun Wang, Rongjuan Pei, Jizheng Chen, Xue Hu, Yuan Zhou, Mengji Lu, Xinwen Chen
Ceruloplasmin (CP) is mainly synthesized by hepatocytes and plays an essential role in iron metabolism. Previous reports have shown that CP levels correlate negatively with disease progression in patients with chronic hepatitis B. However, the function of CP in the hepatitis B virus (HBV) life cycle and the mechanism underlying the above correlation remain unclear. Here, we report that CP can selectively inhibit the production of extracellular HBV virions without altering intracellular viral replication. HBV expression can also downregulate the expression of CP...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28677645/hepatitis-delta-virus-replication-strategy-and-upcoming-therapeutic-options-for-a-neglected-human-pathogen
#8
REVIEW
Florian A Lempp, Stephan Urban
The human Hepatitis Delta Virus (HDV) is unique among all viral pathogens. Encoding only one protein (Hepatitis Delta Antigen; HDAg) within its viroid-like self-complementary RNA, HDV constitutes the smallest known virus in the animal kingdom. To disseminate in its host, HDV depends on a helper virus, the human Hepatitis B virus (HBV), which provides the envelope proteins required for HDV assembly. HDV affects an estimated 15-20 million out of the 240 million chronic HBV-carriers and disperses unequally in disparate geographical regions of the world...
July 4, 2017: Viruses
https://www.readbyqxmd.com/read/28662289/genome-wide-association-analysis-identifies-a-glul-haplotype-for-familial-hepatitis-b-virus-related-hepatocellular-carcinoma
#9
You-Yu Lin, Ming-Whei Yu, Shi-Ming Lin, Shou-Dong Lee, Chih-Ling Chen, Ding-Shinn Chen, Pei-Jer Chen
BACKGROUND: A family history of liver cancer increases the risk of developing hepatocellular carcinoma (HCC) by 2-fold to 10-fold among patients with chronic hepatitis B virus (HBV). Previous genome-wide association studies have identified many possible susceptible loci associated with sporadic HBV-related HCC. However, despite family history being a well-known risk factor for HBV-related HCC, to the authors' knowledge its genetic mechanisms and associating loci remain largely unknown or unexplored, most likely due to the relative rarity of familial HCC and the difficulty of sample collection...
June 29, 2017: Cancer
https://www.readbyqxmd.com/read/28650402/hiv-hbv-co-infection-is-a-significant-risk-factor-for-liver-fibrosis-in-tanzanian-hiv-infected-adults
#10
Claudia Hawkins, Beatrice Christian, Emanuel Fabian, Irene Macha, Cecilia Gawile, Shida Mpangala, Nzovu Ulenga, Chloe L Thio, Lauren Rose Ammerman, Ferdinand Mugusi, Wafaie Fawzi, Richard Green, Robert Murphy
BACKGROUND: In sub-Saharan Africa, the burden of liver disease associated with chronic hepatitis B (HBV) and HIV is unknown. We characterized liver disease using aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 in patients with HIV, HBV, and HIV/HBV co-infection in Tanzania. METHODS: Using a cross sectional design, we compared the prevalence of liver fibrosis in treatment-naive HIV mono-infected, HBV mono-infected, and HIV/HBV co-infected adults enrolled at Management and Development for Health (MDH)-supported HIV treatment clinics in Dar es Salaam, Tanzania...
June 22, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28645725/cell-surface-n-glycan-alteration-in-hepad38-cell-lines-expressing-hepatitis-b-virus
#11
Surya Agung Priyambada, Ryo Misaki, Toru Okamoto, Yuta Okamoto, Takao Ohashi, Keiji Ueda, Yoshiharu Matsuura, Kazuhito Fujiyama
Hepatitis B virus (HBV) is the smallest partially double-stranded DNA virus known to infect humans. Worldwide, more than 50% of hepatocellular carcinoma (HCC) cases are related to chronic Hepatitis B. Development of HCC from normal liver cells is characterized by changes in cell surface N-glycans, which can promote the invasive behavior of tumor cells, leading ultimately to the progression of cancer. However, little is understood about the cell surface N-glycans of HBV-infected liver cells. We try to address this by taking advantage of the HepAD38 cell line, which can replicate HBV in the absence of tetracycline [tet(-)] in growth medium...
June 20, 2017: Virus Research
https://www.readbyqxmd.com/read/28637752/identification-of-intermediate-in-hepatitis-b-virus-ccc-dna-formation-and-sensitive-and-selective-ccc-dna-detection
#12
Jun Luo, Xiuji Cui, Lu Gao, Jianming Hu
The hepatitis B virus (HBV) covalently closed circular (CCC) DNA functions as the only viral template capable of coding for all the viral RNA species and is thus essential to initiate and sustain viral replication. CCC DNA is converted, in a multi-step and ill-understood process, from a relaxed circular (RC) DNA, in which neither of the two DNA strands is covalently closed. To detect putative intermediates during RC to CCC DNA conversion, two 3' exonucleases Exo I and Exo III, in combination were used to degrade all DNA strands with a free 3' end, which would nevertheless preserve closed circular DNA, either single-stranded (SS) or double-stranded (DS)...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28635671/rab33b-controls-hepatitis-b-virus-assembly-by-regulating-core-membrane-association-and-nucleocapsid-processing
#13
Christina Bartusch, Tatjana Döring, Reinhild Prange
Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the secretion of HBV subviral envelope particles, its knockdown reduced the virus yield to 20% and inhibited nucleocapsid (NC) formation and/or NC trafficking. The overexpression of a GDP-restricted Rab33B mutant phenocopied the effect of deficit Rab33B, indicating that Rab33B-specific effector proteins may be involved...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28634402/enhanced-antiviral-and-antifibrotic-effects-of-short-hairpin-rnas-targeting-hbv-and-tgf-%C3%AE-in-hbv-persistent-mice
#14
Lei Ye, Fangming Kan, Tao Yan, Jiaqi Cao, Leiliang Zhang, Zhijian Wu, Wuping Li
The hepatitis B virus (HBV) causes acute and chronic liver infection, which may lead to liver cirrhosis and hepatocellular carcinoma. Current treatments including interferons and nucleotide analogs, have limited therapeutic effects, underscoring the need to identify effective therapeutic options to inhibit HBV replication and prevent complications. Previous animal models mimicking chronic HBV infection do not faithfully reflect disease progression in humans. Here, we used our established HBV-persistent mouse line with liver fibrosis to evaluate the efficacy of novel therapies...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632964/long-term-follow-up-of-patients-triply-infected-with-hiv-and-hepatitis-b-and-c-viruses-in-a-comprehensive-hospital-in-central-china
#15
Rongrong Yang, Xien Gui, Yong Xiong, Shicheng Gao
The clinical characteristics of patients triply infected with HIV, HBV and HCV are notable. From January 2005 to June 2014, a total of 115 cART-naive HIV/HBV/HCV infected individuals were studied and 91 of them were followed-up consecutively after cART with 3TC. After cART with 3TC, the HBV-DNA positive rate decreased from 37.4% (43/115) to 9.9% (9/91) (P<0.001), whereas the HCV-RNA positive rate increased from 53.9% (62/115) to 70.3% (64/91) (P=0.016), and HCV-RNA level increased from 3.52 log10 copies/ml to 4...
June 20, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28628133/hbv-rna-pre-genome-encodes-specific-motifs-that-mediate-interactions-with-the-viral-core-protein-that-promote-nucleocapsid-assembly
#16
Nikesh Patel, Simon J White, Rebecca F Thompson, Richard Bingham, Eva U Weiß, Daniel P Maskell, Adam Zlotnick, Eric Dykeman, Roman Tuma, Reidun Twarock, Neil A Ranson, Peter G Stockley
Formation of the hepatitis B virus nucleocapsid is an essential step in the viral lifecycle, but its assembly is not fully understood. We report the discovery of sequence-specific interactions between the viral pre-genome and the hepatitis B core protein that play roles in defining the nucleocapsid assembly pathway. Using RNA SELEX and bioinformatics, we identified multiple regions in the pre-genomic RNA with high affinity for core protein dimers. These RNAs form stem-loops with a conserved loop motif that trigger sequence-specific assembly of virus-like particles (VLPs) at much higher fidelity and yield than in the absence of RNA...
June 19, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28627822/development-of-a-one-step-reverse-transcription-loop-mediated-isothermal-amplification-system-for-a-highly-sensitive-detection-of-rabbit-hepatitis-e-virus
#17
Jing Wang, Hua Zhang, Shengyuan Yan, Yichao Wang, Xin Lu, Hongwei Fu
BACKGROUND: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis in areas with poor sanitation. Rabbit is one of important animal reservoirs of the virus. Reverse transcription-loop-mediated isothermal amplification (RT-LAMP) system is a novel nucleic acid amplification assay, for which the specificity and sensitivity are much higher than that of conventional PCR. However, previously reported RT-LAMP system cannot detect rabbit HEV, which was identified recently and seems to be another potential source of human HEV infection...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28624194/sustained-inhibition-of-hbv-replication-in%C3%A2-vivo-after-systemic-injection-of-aavs-encoding-artificial-antiviral-primary-micrornas
#18
Mohube Betty Maepa, Abdullah Ely, Wayne Grayson, Patrick Arbuthnot
Chronic infection with hepatitis B virus (HBV) remains a problem of global significance and improving available treatment is important to prevent life-threatening complications arising in persistently infected individuals. HBV is susceptible to silencing by exogenous artificial intermediates of the RNA interference (RNAi) pathway. However, toxicity of Pol III cassettes and short duration of silencing by effectors of the RNAi pathway may limit anti-HBV therapeutic utility. To advance RNAi-based HBV gene silencing, mono- and trimeric artificial primary microRNAs (pri-miRs) derived from pri-miR-31 were placed under control of the liver-specific modified murine transthyretin promoter...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28623307/both-interferon-alpha-and-lambda-can-reduce-all-intrahepatic-hdv-infection-markers-in-hbv-hdv-infected-humanized-mice
#19
Katja Giersch, Maria Homs, Tassilo Volz, Martina Helbig, Lena Allweiss, Ansgar W Lohse, Jörg Petersen, Maria Buti, Teresa Pollicino, Camille Sureau, Maura Dandri, Marc Lütgehetmann
Co-infection with hepatitis B (HBV) and D virus (HDV) is associated with the most severe course of liver disease. Interferon represents the only treatment currently approved. However, knowledge about the impact of interferons on HDV in human hepatocytes is scant. Aim was to assess the effect of pegylated interferon alpha (peg-IFNα) and lambda (peg-IFNλ), compared to the HBV-polymerase inhibitor entecavir (ETV) on all HDV infection markers using human liver chimeric mice and novel HDV strand-specific qRT-PCR and RNA in situ hybridization assays, which enable intrahepatic detection of HDV RNA species...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28614380/interleukin-34-inhibits-hepatitis-b-virus-replication-in-vitro-and-in-vivo
#20
Sheng-Tao Cheng, Hua Tang, Ji-Hua Ren, Xiang Chen, Ai-Long Huang, Juan Chen
BACKGROUND: The hepatitis B virus (HBV) infection could activate the immune system and induce extensive inflammatory response. As the most important inflammatory factor, interleukins are critical for anti-viral immunity. Here we investigated whether interleukin-34 (IL-34) play a role in HBV infection. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we first found that both serum IL-34 and IL-34 mRNA in PBMCs in chronic HBV patients was significantly decreased compared to the healthy controls...
2017: PloS One
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