Public broadly neutralizing antibodies against hepatitis B virus in individuals with elite serologic activity

SUMMARYAlthough there is no effective cure for chronic hepatitis B virus (HBV) infection, antibodies are protective and constitute clinical correlates of recovery from infection. To examine the human neutralizing antibody response to HBV in elite neutralizers we screened 144 individuals. The top individuals produced shared clones of broadly neutralizing antibodies (bNAbs) that targeted 3 non-overlapping epitopes on the HBV S antigen (HBsAg). Single bNAbs protected humanized mice against infection, but selected for resistance mutations in mice with established infection. In contrast, infection was controlled by a combination of bNAbs targeting non-overlapping epitopes with complementary sensitivity to mutations that commonly emerge during human infection. The co-crystal structure of one of the bNAbs with a peptide epitope containing residues frequently mutated in human immune escape variants revealed a loop anchored by oppositely charged residues. The structure provides a molecular explanation for why immunotherapy for HBV infection may require combinations of complementary bNAbs.

Download Full-text

High prevalence of occult hepatitis C virus infection in patients with chronic hepatitis B virus infection

Journal of Medical Microbiology ◽

10.1099/jmm.0.058297-0 ◽

2013 ◽

Vol 62 (8) ◽

pp. 1235-1238 ◽

Cited By ~ 6

Author(s):

Inmaculada Castillo ◽

Javier Bartolomé ◽

Juan Antonio Quiroga ◽

Vicente Carreño

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Virus Infection ◽

Hepatitis B ◽

Hcv Infection ◽

Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus

Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV RNA was tested for in the liver samples of 52 patients with chronic HBV infection and 21 (40 %) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.

Download Full-text

Creation of a Six-fingered Artificial Transcription Factor That Represses the Hepatitis B Virus HBx Gene Integrated into a Human Hepatocellular Carcinoma Cell Line

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057112463066 ◽

2012 ◽

Vol 18 (4) ◽

pp. 378-387 ◽

Cited By ~ 7

Author(s):

Xinghui Zhao ◽

Zhanzhong Zhao ◽

Junwei Guo ◽

Peitang Huang ◽

Xudong Zhu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transcription Factor ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Cell Line ◽

Hbv Infection ◽

Luciferase Reporter ◽

Artificial Transcription Factor ◽

Chronic Hepatitis B Virus ◽

B Virus

Chronic hepatitis B virus (HBV) infection is an independent risk factor for the development of hepatocellular carcinoma (HCC). The HBV HBx gene is frequently identified as an integrant in the chromosomal DNA of patients with HCC. HBx encodes the X protein (HBx), a putative viral oncoprotein that affects transcriptional regulation of several cellular genes. Therefore, HBx may be an ideal target to impede the progression of HBV infection–related HCC. In this study, integrated HBx was transcriptionally downregulated using an artificial transcription factor (ATF). Two three-fingered Cys2-His2 zinc finger (ZF) motifs that specifically recognized two 9-bp DNA sequences regulating HBx expression were identified from a phage-display library. The ZF domains were linked into a six-fingered protein that specified an 18-bp DNA target in the Enhancer I region upstream of HBx. This DNA-binding domain was fused with a Krüppel-associated box (KRAB) transcriptional repression domain to produce an ATF designed to downregulate HBx integrated into the Hep3B HCC cell line. The ATF significantly repressed HBx in a luciferase reporter assay. Stably expressing the ATF in Hep3B cells resulted in significant growth arrest, whereas stably expressing the ATF in an HCC cell line lacking integrated HBx (HepG2) had virtually no effect. The targeted downregulation of integrated HBx is a promising novel approach to inhibiting the progression of HBV infection–related HCC.

Download Full-text

What are the effects of Radix Sophorae Flavescentis in people with chronic hepatitis B virus (HBV) infection?

Cochrane Clinical Answers ◽

10.1002/cca.2599 ◽

2019 ◽

Author(s):

Jane Burch ◽

Deepak Singh-Ranger

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Hepatitis B ◽

Hbv Infection ◽

Chronic Hepatitis B Virus ◽

B Virus

Download Full-text

Discovery of novel hepatitis B virus (HBV) antivirals and analysis of mechanisms of action of HBV-targeting agents

10.32469/10355/70421 ◽

2017 ◽

Author(s):

◽

Andrew Douglas Huber

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Treatment Options ◽

Mechanisms Of Action ◽

Hbv Infection ◽

Viral Inhibition ◽

University Of Missouri ◽

Chronic Hepatitis B Virus ◽

B Virus

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Chronic hepatitis B virus (HBV) infection leads to liver disease, cirrhosis, and hepatocellular carcinoma. Globally, an estimated 50% of all hepatocellular carcinoma cases are linked to chronic HBV infection. More than 240 million people are chronically infected, and there are 0.5-1 million deaths per year due to HBVrelated liver conditions. HBV treatment options rarely cure infections and are associated with adverse side effects that often outweigh the potential benefits of treatment. New treatments, therefore, are highly desired for HBV therapy. Towards this goal, we have developed novel compounds targeting two viral targets and assessed the mechanisms of action by which these compounds act. We have developed systems for the discovery and evaluation of compounds that inhibit 2 distinct steps in the HBV life cycle. Using these systems, we have developed potent inhibitors of HBV replication that have potential to become clinically used HBV drugs. Furthermore, we have used our methods to evaluate which properties of these compounds are likely to result in better viral inhibition. The work described in this thesis has led to at least 2 new compound groups for potential use as HBV antivirals and provides insight into mechanisms by which potent antivirals can be achieved.

Download Full-text

Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine

Hepatology ◽

10.1002/hep.26132 ◽

2013 ◽

Vol 57 (4) ◽

pp. 1303-1313 ◽

Cited By ~ 39

Author(s):

Elodie Beaumont ◽

Romuald Patient ◽

Christophe Hourioux ◽

Isabelle Dimier-Poisson ◽

Philippe Roingeard

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Neutralizing Antibodies ◽

Prophylactic Vaccine ◽

Virus Hepatitis ◽

Broadly Neutralizing Antibodies ◽

Virus Envelope ◽

B Virus

Download Full-text

Pregnancy Complicated With Hepatitis B Virus Infection and Preterm Birth: A Retrospective Cohort Study

10.21203/rs.3.rs-152431/v1 ◽

2021 ◽

Author(s):

Shuisen Zheng ◽

Huale Zhang ◽

Rongxin Chen ◽

Jianying Yan ◽

Qing Han

Keyword(s):

Risk Factor ◽

Preterm Birth ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Pregnant Women ◽

Hbv Infection ◽

Confounding Factors ◽

Logistics Regression ◽

Chronic Hepatitis B Virus ◽

B Virus

Abstract Background: We aimed to investigate whether maternal chronic hepatitis B virus (HBV) infection affects preterm birth（PTB) in pregnant women. Methods: We retrospectively analyzed HBV-infected and non-infected pregnant women attending antenatal care at Fujian Provincial Maternity and Child Health Hospital, Fuzhou, China between January 1, 2016 to December 31, 2018. Participants were divided into HBV infection (n = 1302) and control (n = 12813) groups. We compared baseline data, pregnancy and perinatal complications, and preterm delivery outcomes between groups and performed subgroup comparisons and multiple logistics regression analysis to adjust for confounding factors. Results: The incidence of PTBs before 37 weeks was similar between the groups. PTBs before 34 weeks were significantly more among the HBV infection group than among the controls (1.6% VS. 0.8% ; P = 0.003) After adjusting for confounding factors through logistics regression, HBV infection was found to be an independent PTB risk factor before 34 weeks gestation (adjusted odds ratio 1.796; 95% confidence interval[1.071, 3.012]). According to the subgroup analysis based on whether hepatitis B e-antigen (HBeAg) was positive and whether alanine aminotransferase (ALT) levels were normal during the second trimester, PTB was more frequent in HBeAg negative HBV infection before 34 weeks than among controls(1.8% VS. 0.8%). The PTB rate for pregnant women with normal ALT and HBV infection before 34 weeks was higher than that of the controls (1.6% VS. 0.8%) Conclusion HBV infection is an independent risk factor for PTB before 34 weeks. Comprehensive programs focusing on pregnant women with HBV infection would reduce the incidence of adverse outcomes.

Download Full-text