Host Transcription Factors in Hepatitis B Virus RNA Synthesis

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Abstract

The hepatitis B virus (HBV) chronically infects over 250 million people worldwide and is one of the leading causes of liver cancer and hepatocellular carcinoma. HBV persistence is due in part to the highly stable HBV minichromosome or HBV covalently closed circular DNA (cccDNA) that resides in the nucleus. As HBV replication requires the help of host transcription factors to replicate, focusing on host protein–HBV genome interactions may reveal insights into new drug targets against cccDNA. The structural details on such complexes, however, remain poorly defined. In this review, the current literature regarding host transcription factors’ interactions with HBV cccDNA is discussed.

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Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Huan Yan, Guocai Zhong, Guangwei Xu … (2012)

Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV. DOI: http://dx.doi.org/10.7554/eLife.00049.001

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Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4.

Lisa Cirillo, Frank Robert Lin, Isabel Cuesta … (2002)

The transcription factors HNF3 (FoxA) and GATA-4 are the earliest known to bind the albumin gene enhancer in liver precursor cells in embryos. To understand how they access sites in silent chromatin, we assembled nucleosome arrays containing albumin enhancer sequences and compacted them with linker histone. HNF3 and GATA-4, but not NF-1, C/EBP, and GAL4-AH, bound their sites in compacted chromatin and opened the local nucleosomal domain in the absence of ATP-dependent enzymes. The ability of HNF3 to open chromatin is mediated by a high affinity DNA binding site and by the C-terminal domain of the protein, which binds histones H3 and H4. Thus, factors that potentiate transcription in development are inherently capable of initiating chromatin opening events.

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Transcription factors in long-term memory and synaptic plasticity.

Cristina Alberini (2009)

Transcription is a molecular requisite for long-term synaptic plasticity and long-term memory formation. Thus, in the last several years, one main interest of molecular neuroscience has been the identification of families of transcription factors that are involved in both of these processes. Transcription is a highly regulated process that involves the combined interaction and function of chromatin and many other proteins, some of which are essential for the basal process of transcription, while others control the selective activation or repression of specific genes. These regulated interactions ultimately allow a sophisticated response to multiple environmental conditions, as well as control of spatial and temporal differences in gene expression. Evidence based on correlative changes in expression, genetic mutations, and targeted molecular inhibition of gene expression have shed light on the function of transcription in both synaptic plasticity and memory formation. This review provides a brief overview of experimental work showing that several families of transcription factors, including CREB, C/EBP, Egr, AP-1, and Rel, have essential functions in both processes. The results of this work suggest that patterns of transcription regulation represent the molecular signatures of long-term synaptic changes and memory formation.

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Journal ID (nlm-ta): Viruses

Journal ID (iso-abbrev): Viruses

Journal ID (publisher-id): viruses

Title: Viruses

Publisher: MDPI

ISSN (Electronic): 1999-4915

Publication date (Electronic): 30 January 2020

Publication date Collection: February 2020

Volume: 12

Issue: 2

Electronic Location Identifier: 160

Affiliations

[1 ]Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Dr. W., Lethbridge, AB T1K 3M4, Canada; kristi.turton@ 123456uleth.ca (K.L.T.); vmeierstephenson@ 123456gmail.com (V.M.-S.); maulik.badmalia@ 123456uleth.ca (M.D.B.)

[2 ]Department of Microbiology, Immunology and Infectious Diseases, Cumming, School of Medicine, University of Calgary, 2500 University Dr. N.W., Calgary, AB T2N 1N4, Canada; cscoffin@ 123456ucalgary.ca

[3 ]Department of Medicine, Division of Gastroenterology and Hepatology, University of Calgary, 1403 29 St. N.W., Calgary, AB T2N 2T9, Canada

[4 ]Discovery Lab, Faculty of Medicine & Dentistry, and the Li Ka Shing Institute of Virology, University of Alberta, 6-010 Katz Center for Health Research, Edmonton, AB T6G 2E1, Canada

Author notes

[* ]Correspondence: trushar.patel@ 123456uleth.ca

Author information

Kristi L. Turton https://orcid.org/0000-0003-1926-8907

Vanessa Meier-Stephenson https://orcid.org/0000-0003-4004-4940

Trushar R. Patel https://orcid.org/0000-0003-0627-2923

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Publisher ID: viruses-12-00160

DOI: 10.3390/v12020160

PMC ID: 7077322

PubMed ID: 32019103

SO-VID: 2a591aef-5ecb-4830-b048-acb45e0c57ad

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Host Transcription Factors in Hepatitis B Virus RNA Synthesis

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Abstract

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Point-Of-Care Testing for Hepatitis

Most cited references 252

Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4.

Transcription factors in long-term memory and synaptic plasticity.

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