Dataset Information

Phosphorylation of the Arginine-Rich C-Terminal Domains of the Hepatitis B Virus (HBV) Core Protein as a Fine Regulator of the Interaction between HBc and Nucleic Acid.

ABSTRACT: The morphogenesis of Hepatitis B Virus (HBV) viral particles is nucleated by the oligomerization of HBc protein molecules, resulting in the formation of an icosahedral capsid shell containing the replication-competent nucleoprotein complex made of the viral polymerase and the pre-genomic RNA (pgRNA). HBc is a phospho-protein containing two distinct domains acting together throughout the viral replication cycle. The N-terminal domain, (residues 1-140), shown to self-assemble, is linked by a short flexible domain to the basic C-terminal domain (residues 150-183) that interacts with nucleic acids (NAs). In addition, the C-terminal domain contains a series of phospho-acceptor residues that undergo partial phosphorylation and de-phosphorylation during virus replication. This highly dynamic process governs the homeostatic charge that is essential for capsid stability, pgRNA packaging and to expose the C-terminal domain at the surface of the particles for cell trafficking. In this review, we discuss the roles of the N-terminal and C-terminal domains of HBc protein during HBV morphogenesis, focusing on how the C-terminal domain phosphorylation dynamics regulate its interaction with nucleic acids throughout the assembly and maturation of HBV particles.

SUBMITTER: de Rocquigny H

PROVIDER: S-EPMC7412469 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Phosphorylation of the Arginine-Rich C-Terminal Domains of the Hepatitis B Virus (HBV) Core Protein as a Fine Regulator of the Interaction between HBc and Nucleic Acid.

de Rocquigny Hugues H Rat Virgile V Pastor Florentin F Darlix Jean Luc JL Hourioux Christophe C Roingeard Philippe P

Viruses 20200708 7

The morphogenesis of Hepatitis B Virus (HBV) viral particles is nucleated by the oligomerization of HBc protein molecules, resulting in the formation of an icosahedral capsid shell containing the replication-competent nucleoprotein complex made of the viral polymerase and the pre-genomic RNA (pgRNA). HBc is a phospho-protein containing two distinct domains acting together throughout the viral replication cycle. The N-terminal domain, (residues 1-140), shown to self-assemble, is linked by a short ...[more]

PMID: 32650547

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Project description:Hepatitis B virus (HBV) DNA replication occurs within the HBV icosahedral core particles. HBV core protein (HBc) contains an arginine-rich domain (ARD) at its carboxyl terminus. This ARD domain of HBc 149-183 is known to be important for viral replication but not known to have a structure. Recently, nucleocapsid proteins of several viruses have been shown to contain nucleic acid chaperone activity, which can facilitate structural rearrangement of viral genome. Major features of nucleic acid chaperones include highly basic amino acid residues and flexible protein structure. To test the nucleic acid chaperone hypothesis for HBc ARD, we first used the disassembled full-length HBc from Escherichia coli to analyze the nucleic acid annealing and strand displacement activities. To exclude the potential contamination of chaperones from E. coli, we designed synthetic HBc ARD peptides with different lengths and serine phosphorylations. We demonstrated that HBc ARD peptide can behave like a bona fide nucleic acid chaperone and that the chaperone activity depends on basic residues of the ARD domain. The loss of chaperone activity by arginine-to-alanine substitutions in the ARD can be rescued by restoring basic residues in the ARD. Furthermore, the chaperone activity is subject to regulation by phosphorylation and dephosphorylation at the HBc ARD. Interestingly, the HBc ARD can enhance in vitro cleavage activity of RNA substrate by a hammerhead ribozyme. We discuss here the potential significance of the HBc ARD chaperone activity in the context of viral DNA replication, in particular, at the steps of primer translocations and circularization of linear replicative intermediates.Hepatitis B virus is a major human pathogen. At present, no effective treatment can completely eradicate the virus from patients with chronic hepatitis B. We report here a novel chaperone activity associated with the viral core protein. Our discovery could lead to a new drug design for more effective treatment against hepatitis B virus in the future.

Project description:BACKGROUND:Due to numerous blood exposures hospital staff are at risk of acquiring hepatitis B virus (HBV) infections. This study aimed at estimating prevalence of HBV, associated risk factors and HBV vaccination among Polish health care workers (HCWs). METHODS:A cross-sectional sero-survey was conducted (October 2016-January 2018) in 10 randomly selected hospitals from two provinces: of low and high incidence of HBV, with the use of an anonymous, self- administered questionnaire. Blood samples were screened for hepatitis B core antibodies (anti-HBc) with enzyme immunoassay. RESULTS:Of the 306 participating HCWs, 88.6% were females, 69.9% nurses (mean age 47.8?±?9.0?years). HBV vaccination was reported by 94.2%, participants (4.7% with 2 doses, 58.1% with 3 doses, 37.2% took a booster), but of these 75.1% reported no post-immunization serology. The sero-prevalence of anti-HBc was 12.1% (95%CI 8.4-15.7%); only 11.1% had ever screened themselves for HBV infection. Out of 37 anti-HBc positive HCWs, 29 reported being vaccinated for HBV; 10.5% vaccinated HCWs were anti-HBc positive. Regarding other occupational risk factors, 27.8% had experienced a sharp injury (SI) in the last year, 80.0% of incidents were not reported. The use of safety devices (SD) was 86.3%; 35.9% participants used to recap a needle. Older age (OR?=?4.24), lack of HBV vaccination (OR?=?7.42), working at the province of high HBV incidence in the general population (OR?=?2.69) were each predictors of participant's HBV infection. CONCLUSIONS:High anti-HBc seroprevalence was found in hospital staff with older generation particularly constituting a risk group. Unsatisfactory vaccination coverage and the use of SDs, needle recapping and under-reporting of SIs were main modifiable risk factors regarding HBV infection. The study provides evidence of the protective role of HBV vaccine, as well as the possible effect of HBV incidence in the general population on HCW's anti-HBc seropositivity. Universal vaccination, followed by strict policies to confirm immunity, better compliance with infection-control practices and widespread implementation of SDs should be enforced to protect hospital staff from occupationally acquired HBV infections.

Dataset Information

Phosphorylation of the Arginine-Rich C-Terminal Domains of the Hepatitis B Virus (HBV) Core Protein as a Fine Regulator of the Interaction between HBc and Nucleic Acid.

Publications

Phosphorylation of the Arginine-Rich C-Terminal Domains of the Hepatitis B Virus (HBV) Core Protein as a Fine Regulator of the Interaction between HBc and Nucleic Acid.

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