Proc Natl Acad Sci U S A
Department of Infectious Diseases, Novartis Institutes for BioMedical Research, Emeryville, CA 94608.
Published: October 2015
Chronic hepatitis B virus (HBV) infection affects 240 million people worldwide and is a major risk factor for liver failure and hepatocellular carcinoma. Current antiviral therapy inhibits cytoplasmic HBV genomic replication, but is not curative because it does not directly affect nuclear HBV closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence. Novel approaches that directly target cccDNA regulation would therefore be highly desirable. cccDNA is assembled with cellular histone proteins into chromatin, but little is known about the regulation of HBV chromatin by histone posttranslational modifications (PTMs). Here, using a new cccDNA ChIP-Seq approach, we report, to our knowledge, the first genome-wide maps of PTMs in cccDNA-containing chromatin from de novo infected HepG2 cells, primary human hepatocytes, and from HBV-infected liver tissue. We find high levels of PTMs associated with active transcription enriched at specific sites within the HBV genome and, surprisingly, very low levels of PTMs linked to transcriptional repression even at silent HBV promoters. We show that transcription and active PTMs in HBV chromatin are reduced by the activation of an innate immunity pathway, and that this effect can be recapitulated with a small molecule epigenetic modifying agent, opening the possibility that chromatin-based regulation of cccDNA transcription could be a new therapeutic approach to chronic HBV infection.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4620859 | PMC |
http://dx.doi.org/10.1073/pnas.1518090112 | DOI Listing |
Hepatol Commun
February 2025
Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
The global epidemiology of HCC is shifting due to changes in both established and emerging risk factors. This transformation is marked by an emerging prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes, alongside traditional risks such as viral hepatitis (HBV and HCV), and exposure to chemical agents like aflatoxin, alcohol, tobacco, and air pollution. This review examines how environmental exposures and evolving liver pathology, exacerbated by lifestyle and metabolic conditions, are contributing to the rising worldwide incidence of HCC.
View Article and Find Full Text PDFVaccine X
January 2025
Reference Center for Gender-specific Medicine, Istituto Superiore di Sanità [Italian National Institute of Health], Rome, Italy.
Globally, healthcare workers (HCWs) are at greater risk of contracting Hepatitis B virus (HBV) infection than the general population, due to their frequent contact with blood or body fluids. For this reason, WHO underlined the importance of HBV immunization for all HCWs. Although sex is now considered one of the key factors influencing the intensity and duration of the immune response to vaccines, sex-specific analysis of vaccine-induced anti-HBs antibodies is rarely conducted.
View Article and Find Full Text PDFWorld J Gastroenterol
January 2025
Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
In this editorial, we comment on the article by Meng . Chronic hepatitis B (CHB) is a significant global health problem, particularly in developing countries. Hepatitis B virus (HBV) infection is one of the most important risk factors for cirrhosis and hepatocellular carcinoma.
View Article and Find Full Text PDFGMS Hyg Infect Control
December 2024
Uzun Mehmet Chest and Work Diseases Hospital, Medical Microbiology Dept, Zonguldak, Turkey.
Background: The use of laryngeal masks (LM) has increased widely today, both in anesthesia and in emergency cases. LM are available as reusable and disposable. Although reuse of disposable LM is not recommended, they are reused again after decontamination with different methods in anesthesia units in some countries.
View Article and Find Full Text PDFActa Neurochir (Wien)
January 2025
Department of Neurosurgery, Hebei General Hospital, 348# Heping Road, Shijiazhuang City, 050000, Hebei Province, China.
Objective: To explore the correlation between posterior fossa crowding and the occurrence of classical trigeminal neuralgia (TN).
Methods: A total of 60 patients diagnosed with classical TN and 60 age- and sex-matched healthy volunteers were included as a control group for a case-control study. All subjects underwent high-resolution 3D magnetic resonance imaging (MRI) examinations (including 3D-FIESTA and 3D-TOF MRA sequences).
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.