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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

Authors
Jung, J; Kim, HY; Kim, T; Shin, BH; Park, GS; Park, S; Chwae, YJ; Shin, HJ; Kim, K
Citation
PloS one, 7(7):e41087-e41087, 2012
Journal Title
PloS one
ISSN
1932-6203
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.
MeSH terms
Amino Acid SequenceAmino Acid SubstitutionAnimalsArginine/*chemistryCell LineDNA ReplicationDNA, ViralHepatitis B Virus, Duck/*physiologyHepatitis B virus/*physiologyHumansMolecular Sequence DataMutant Chimeric Proteins/chemistry/metabolismProtein Binding*Protein Interaction Domains and MotifsRNA/metabolismRNA, Viral/metabolismViral Core Proteins/*chemistry*Virus Replication
DOI
10.1371/journal.pone.0041087
PMID
22911745
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
박, 선최, 용준신, 호준김, 경민
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