scholarly journals A pocket-factor–triggered conformational switch in the hepatitis B virus capsid

2021 ◽  
Vol 118 (17) ◽  
pp. e2022464118
Author(s):  
Lauriane Lecoq ◽  
Shishan Wang ◽  
Marie Dujardin ◽  
Peter Zimmermann ◽  
Leonard Schuster ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Protein ◽  
Hot Spot ◽  
Protein A ◽  
Structural Variations ◽  
Interaction Hypothesis ◽  
B Virus ◽  
Alternative Conformation ◽  
Main Culprit

Viral hepatitis is growing into an epidemic illness, and it is urgent to neutralize the main culprit, hepatitis B virus (HBV), a small-enveloped retrotranscribing DNA virus. An intriguing observation in HB virion morphogenesis is that capsids with immature genomes are rarely enveloped and secreted. This prompted, in 1982, the postulate that a regulated conformation switch in the capsid triggers envelopment. Using solid-state NMR, we identified a stable alternative conformation of the capsid. The structural variations focus on the hydrophobic pocket of the core protein, a hot spot in capsid–envelope interactions. This structural switch is triggered by specific, high-affinity binding of a pocket factor. The conformational change induced by the binding is reminiscent of a maturation signal. This leads us to formulate the “synergistic double interaction” hypothesis, which explains the regulation of capsid envelopment and indicates a concept for therapeutic interference with HBV envelopment.

scholarly journals Hepatitis B Virus DNA Replication Is Coordinated by Core Protein Serine Phosphorylation and HBx Expression

2005 ◽  
Vol 79 (15) ◽  
pp. 9810-9820 ◽  
Author(s):  
Margherita Melegari ◽  
Sarah K. Wolf ◽  
Robert J. Schneider
Keyword(s):  
Hepatitis B Virus ◽  
Dna Replication ◽  
Hepatitis B ◽  
Viral Replication ◽  
Core Protein ◽  
Regulatory Protein ◽  
Protein A ◽  
Serine Phosphorylation ◽  
Hbv Replication ◽  
B Virus

ABSTRACT The hepatitis B virus (HBV) core protein forms the capsid of viral particles and is essential for viral genome DNA replication and maturation. The C terminus of core protein contains three serines at positions 155, 162, and 170, phosphorylation of which is important for viral DNA replication. We demonstrate that the phosphorylation of these serines is stimulated by the viral HBx protein, a regulatory protein that activates signal transduction pathways and viral replication. HBx is therefore shown to stimulate HBV replication by increasing core serine phosphorylation. Mutational, biochemical, and mixing studies of C-terminal core serine mutants demonstrate that multiple serine phosphorylations occur on the same core protein. Mutation of individual core protein serines is shown to inhibit HBV replication at distinct stages corresponding to encapsidation of viral pregenomic RNA, reverse transcription, and restriction to synthesis of specific DNA replicative intermediates. We therefore demonstrate that a primary target of HBV replication that is regulated by HBx protein corresponds to increased phosphorylation of the viral core protein. We also demonstrate that core phosphorylation mediated by HBx promotes sequential progression of viral replication through the assembly of capsids primed for different stages of DNA synthesis.

scholarly journals Peptide aptamers targeting the hepatitis B virus core protein: a new class of molecules with antiviral activity

Oncogene ◽  
2001 ◽  
Vol 20 (45) ◽  
pp. 6579-6586 ◽  
Author(s):  
Karin Butz ◽  
Claudia Denk ◽  
Barbara Fitscher ◽  
Irena Crnkovic-Mertens ◽  
Angela Ullmann ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Core Protein ◽  
Protein A ◽  
Peptide Aptamers ◽  
New Class ◽  
Virus Core ◽  
B Virus

scholarly journals RBM24 stabilizes hepatitis B virus pregenomic RNA but inhibits core protein translation by targeting the terminal redundancy sequence

2018 ◽  
Vol 7 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Yongxuan Yao ◽  
Bo Yang ◽  
Huang Cao ◽  
Kaitao Zhao ◽  
Yifei Yuan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Protein ◽  
Protein Translation ◽  
B Virus

scholarly journals Translation of hepatitis B virus (HBV) surface proteins from the HBV pregenome and precore RNAs in Semliki Forest virus-driven expression

2004 ◽  
Vol 85 (11) ◽  
pp. 3343-3351 ◽  
Author(s):  
Anna Zajakina ◽  
Tatyana Kozlovska ◽  
Ruta Bruvere ◽  
Jekaterina Aleksejeva ◽  
Paul Pumpens ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Semliki Forest Virus ◽  
Expression System ◽  
Protein A ◽  
Direct Repeat ◽  
Infection Process ◽  
Surface Proteins ◽  
B Virus ◽  
Internal Translation

Hepatitis B virus (HBV) pregenome RNA (pgRNA) serves as a translation template for the HBV core (HBc) protein and viral polymerase (Pol). HBV precore RNA (pcRNA) directs the synthesis of the precore (preC) protein, a precursor of the hepatitis B e antigen (HBeAg). pgRNA and pcRNA were expressed in the Semliki Forest virus (SFV) expression system. Besides the HBc and preC proteins, there was revealed the synthesis of all three forms of HBV surface (HBs) proteins: long (LHBs), middle (MHBs) and short (SHBs), the start codons of which are located more than 1000 nt downstream of the HBc and preC start codons. Moreover, other HBV templates, such as 3′-truncated pgRNA lacking 3′ direct repeat and Pol mRNA, both carrying internally the HBs sequences, provided the synthesis of three HBs protein forms in the SFV-driven expression system. Maximal production of the HBs was provided by Pol mRNA, while HBc- and preC-producing templates showed relatively low internal translation of the HBs. These data allow the proposal of a ribosome leaky scanning model of internal translation initiation for HBs proteins. The putative functional role of such exceptional synthesis of the HBs proteins from the pgRNA and pcRNA templates in the natural HBV infection process needs further evaluation.

Construction and expression of hepatitis B virus vector encoding TC-tagged core protein

2009 ◽  
Vol 3 (4) ◽  
pp. 396-402 ◽  
Author(s):  
Yuanyuan Lin ◽  
Xiaoming Cheng ◽  
Yuhu Song ◽  
Li Zhou ◽  
Peiyuan Li ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Protein ◽  
Virus Vector ◽  
B Virus
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