Hepatitis B virus direct repeat sequence: Imino proton exchange rates and distance and torsion angle restraints from NMR

Biochemistry ◽  
1994 ◽  
Vol 33 (2) ◽  
pp. 427-438 ◽  
Author(s):  
Karl D. Bishop ◽  
Forrest J. H. Blocker ◽  
William Egan ◽  
Thomas L. James
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Exchange Rates ◽  
Torsion Angle ◽  
Direct Repeat ◽  
Repeat Sequence ◽  
Proton Exchange ◽  
Imino Proton ◽  
Direct Repeat Sequence ◽  
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.

Structural Study of a DNA.cntdot.RNA Hybrid Duplex with a Chiral Phosphorothioate Moiety by NMR: Extraction of Distance and Torsion Angle Constraints and Imino Proton Exchange Rates

Biochemistry ◽  
1994 ◽  
Vol 33 (37) ◽  
pp. 11062-11072 ◽  
Author(s):  
Carlos Gonzalez ◽  
Wojciech Stec ◽  
Anna Kobylanska ◽  
Richard I. Hogrefe ◽  
Mark Reynolds ◽  
...  
Keyword(s):  
Exchange Rates ◽  
Structural Study ◽  
Torsion Angle ◽  
Proton Exchange ◽  
Imino Proton ◽  
Hybrid Duplex ◽  
Imino Proton Exchange

scholarly journals Characterization of the Termini of Cytoplasmic Hepatitis B Virus Deproteinated Relaxed Circular DNA

2020 ◽  
Vol 95 (1) ◽  
Author(s):  
Dawei Cai ◽  
Ran Yan ◽  
Jerry Z. Xu ◽  
Hu Zhang ◽  
Sheng Shen ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Molecular Mechanisms ◽  
Direct Repeat ◽  
Hydroxyl Group ◽  
Viral Polymerase ◽  
Circular Dna ◽  
Phosphodiester Bond ◽  
Covalently Closed Circular Dna ◽  
B Virus

ABSTRACT The biosynthesis of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) requires the removal of the covalently linked viral polymerase from the 5′ end of the minus strand [(−)strand] of viral relaxed circular DNA (rcDNA), which generates a deproteinated rcDNA (DP-rcDNA) intermediate. In the present study, we systematically characterized the four termini of cytoplasmic HBV DP-rcDNA by 5′/3′ rapid amplification of cDNA ends (RACE), 5′ radiolabeling, and exonuclease digestion, which revealed the following observations: (i) DP-rcDNA and rcDNA possess an identical 3′ end of (−)strand DNA; (ii) compared to rcDNA, DP-rcDNA has an extended but variable 3′ end of plus strand [(+)strand] DNA, most of which is in close proximity to direct repeat 2 (DR2); (iii) DP-rcDNA exhibits an RNA primer-free 5′ terminus of (+)strand DNA with either a phosphate or hydroxyl group; and (iv) the 5′ end of the DP-rcDNA (−)strand is unblocked at nucleotide G1828, bearing a phosphate moiety, indicating the complete removal of polymerase from rcDNA via unlinking the tyrosyl-DNA phosphodiester bond during rcDNA deproteination. However, knockout of cellular 5′ tyrosyl-DNA phosphodiesterase 2 (TDP2) did not markedly affect rcDNA deproteination or cccDNA formation. Thus, our work sheds new light on the molecular mechanisms of rcDNA deproteination and cccDNA biogenesis. IMPORTANCE The covalently closed circular DNA (cccDNA) is the persistent form of the hepatitis B virus (HBV) genome in viral infection and an undisputed antiviral target for an HBV cure. HBV cccDNA is converted from viral genomic relaxed circular DNA (rcDNA) through a complex process that involves removing the covalently bound viral polymerase from rcDNA, which produces a deproteinated-rcDNA (DP-rcDNA) intermediate for cccDNA formation. In this study, we characterized the four termini of cytoplasmic DP-rcDNA and compared them to its rcDNA precursor. While rcDNA and DP-rcDNA have an identical 3′ terminus of (−)strand DNA, the 3′ terminus of (+)strand DNA on DP-rcDNA is further elongated. Furthermore, the peculiarities on rcDNA 5′ termini, specifically the RNA primer on the (+)strand and the polymerase on the (−)strand, are absent from DP-rcDNA. Thus, our study provides new insights into a better understanding of HBV rcDNA deproteination and cccDNA biosynthesis.

scholarly journals Subunit exchange rates in Hepatitis B virus capsids are geometry- and temperature-dependent

2010 ◽  
Vol 12 (41) ◽  
pp. 13368 ◽  
Author(s):  
Charlotte Uetrecht ◽  
Norman R. Watts ◽  
Stephen J. Stahl ◽  
Paul T. Wingfield ◽  
Alasdair C. Steven ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Exchange Rates ◽  
Temperature Dependent ◽  
Subunit Exchange ◽  
Virus Capsids ◽  
B Virus

Precore hepatitis B virus carrying lamivudine resistant mutations are not associated with decreassed replication fitness and are sensitive to adefovir

2001 ◽  
Vol 120 (5) ◽  
pp. A64-A64
Author(s):  
R CHEN ◽  
P DESMOND ◽  
W DELANEY ◽  
D COLLEDGE ◽  
R EDWARDS ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Virus ◽  
Replication Fitness

Prevalence and Clinical Implications of Hepatitis B Virus Genotypes in Southern Taiwan

2003 ◽  
Vol 38 (1) ◽  
pp. 95-101 ◽  
Author(s):  
Lee C.-M. ◽  
Chen C.-H. ◽  
Lu S.-N. ◽  
Tung H.-D. ◽  
Chou W.-J. ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Clinical Implications ◽  
B Virus ◽  
Virus Genotypes ◽  
Southern Taiwan

Alkoholabstinenz allein verbessert die Leberfunktion und verlängert das Überleben bei der alkoholischen Lebererkrankung!

2016 ◽  
Vol 62 (6) ◽  
pp. 396-400 ◽  
Author(s):  
Helmut K. Seitz ◽  
Tatjana Arslic-Schmitt
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Virus ◽  
Alkoholische Lebererkrankung ◽  
Alkoholische Steatohepatitis

Zusammenfassung. Zielsetzung: Im Folgenden soll dargelegt werden, dass Alkoholkarenz sowohl die Leberfunktion als auch das Überleben in jedem Stadium einer alkoholischen Lebererkrankung günstig beeinflusst. Ergebnisse: Täglicher Alkoholkonsum von mehr als 25 Gramm reinen Alkohols, etwas mehr als ¼ Liter Wein beim Mann und etwa die Hälfte bei der Frau sind, mit einem erhöhten Risiko für eine alkoholische Lebererkrankung (ALE) behaftet. Die ALE besteht aus einem breiten Spektrum von histopathologischen Veränderungen. Sie beginnt immer mit einer alkoholischen Fettleber, die sich in eine alkoholische Steatohepatitis weiterentwickeln kann. Fortgeschrittene Formen der ALE beinhalten die Leberfibrose, die Leberzirrhose und das hepatozelluläre Karzinom. In der Behandlung jeder Form der ALE ist die Alkoholabstinenz von zentraler Bedeutung. Ein Großteil der alkoholischen Fettlebern bildet sich unter Alkoholkarenz oder sogar Alkoholreduktion zurück. Die alkoholische Hepatitis, ein klinisches Syndrom mit hoher Mortalität, führt ohne Alkoholkarenz innerhalb von Tagen und Wochen zum Tode. Darüber hinaus ist selbst die Leberfibrose (perivenös und perisinusoidal) unter Alkoholkarenz rückbildungsfähig. Bei allen Formen der fortgeschrittenen ALE (kompensiert und nicht-kompensierte Leberzirrhose) wird die Mortalität durch Alkoholkarenz oder signifikante Reduktion im Gegensatz zum fortgesetzten Alkoholkonsum signifikant verringert. Selbst Patienten mit alkoholischer Leberzirrhose können über mehr als 20 Jahre ohne Komplikationen weiterleben, wenn sie komplett auf Alkohol verzichten. Schlussfolgerung: Im Vergleich zu Leberzirrhose anderer Ätiologie, wie zum Beispiel Zirrhosen, die durch das Hepatitis-B Virus oder das Hepatitis-C Virus verursacht sind, haben alkoholische Leberzirrhosen unter Alkoholkarenz eine wesentlich bessere Prognose. Damit ist Alkoholkarenz eine gute Therapie und der Erfolg jeder anderen neuen Therapie muss mit Alkoholkarenz verglichen werden.

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