Dataset Information

C-terminal substitution of HBV core proteins with those from DHBV reveals that arginine-rich 167RRRSQSPRR175 domain is critical for HBV replication.

ABSTRACT: To investigate the contributions of carboxyl-terminal nucleic acid binding domain of HBV core (C) protein for hepatitis B virus (HBV) replication, chimeric HBV C proteins were generated by substituting varying lengths of the carboxyl-terminus of duck hepatitis B virus (DHBV) C protein for the corresponding regions of HBV C protein. All chimeric C proteins formed core particles. A chimeric C protein with 221-262 amino acids of DHBV C protein, in place of 146-185 amino acids of the HBV C protein, supported HBV pregenomic RNA (pgRNA) encapsidation and DNA synthesis: 40% amino acid sequence identity or 45% homology in the nucleic-acid binding domain of HBV C protein was sufficient for pgRNA encapsidation and DNA synthesis, although we predominantly detected spliced DNA. A chimeric C protein with 221-241 and 251-262 amino acids of DHBV C, in place of HBV C 146-166 and 176-185 amino acids, respectively, could rescue full-length DNA synthesis. However, a reciprocal C chimera with 242-250 of DHBV C ((242)RAGSPLPRS(250)) introduced in place of 167-175 of HBV C ((167)RRRSQSPRR(175)) significantly decreased pgRNA encapsidation and DNA synthesis, and full-length DNA was not detected, demonstrating that the arginine-rich (167)RRRSQSPRR(175) domain may be critical for efficient viral replication. Five amino acids differing between viral species (underlined above) were tested for replication rescue; R169 and R175 were found to be important.

SUBMITTER: Jung J

PROVIDER: S-EPMC3401125 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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C-terminal substitution of HBV core proteins with those from DHBV reveals that arginine-rich 167RRRSQSPRR175 domain is critical for HBV replication.

Jung Jaesung J Kim Hee-Young HY Kim Taeyeung T Shin Bo-Hye BH Park Gil-Soon GS Park Sun S Chwae Yong-Joon YJ Shin Ho-Joon HJ Kim Kyongmin K

PloS one 20120720 7

To investigate the contributions of carboxyl-terminal nucleic acid binding domain of HBV core (C) protein for hepatitis B virus (HBV) replication, chimeric HBV C proteins were generated by substituting varying lengths of the carboxyl-terminus of duck hepatitis B virus (DHBV) C protein for the corresponding regions of HBV C protein. All chimeric C proteins formed core particles. A chimeric C protein with 221-262 amino acids of DHBV C protein, in place of 146-185 amino acids of the HBV C protein, ...[more]

PMID: 22911745

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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.

Dataset Information

C-terminal substitution of HBV core proteins with those from DHBV reveals that arginine-rich 167RRRSQSPRR175 domain is critical for HBV replication.

Publications

C-terminal substitution of HBV core proteins with those from DHBV reveals that arginine-rich 167RRRSQSPRR175 domain is critical for HBV replication.

Similar Datasets

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