scholarly journals The variability of amino acids sequences in hepatitis B virus

2018 ◽  
Author(s):  
Jianhao Cao ◽  
Shuhong Luo ◽  
Yuanyan Xiong
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Assembly ◽  
Amino Acid Level ◽  
Alpha Helix ◽  
Amino Acid Sequences ◽  
Immune Recognition ◽  
B Virus

AbstractHepatitis B virus (HBV) is an important human pathogen belonging to theHepadnaviridaefamily,Orthohepadnavirusgenus. It infects over 240 million people globally. The reverse transcription during its genome replication leads to low fidelity DNA synthesis, which is the source of variability in the viral proteins. To investigate the variability quantitatively, we retrieved amino acid sequences of 5167 records of all available HBV genotypes (A-J) from the Genbank database. The amino acid sequences encoded by the open reading frames (ORF) S/C/P/X in the HBV genome were extracted and subjected to alignment respectively. We analyzed the variability of the lengths and the sequences of proteins as well as the frequencies of amino acids. Our study comprehensively characterized of the variability and conservation of HBV at the level of amino acids, especially for the structural proteins, hepatitis B surface antigens (HBsAg), to find out the potential sites critical for virus assembly and immune recognition. Interestingly, the preS1/S2 domains in HBsAg were variable at some positions of amino acid residues, which provides a potential mechanism of immune-escape for HBV, while the preS2 and S domains were conserved in the lengths of protein sequences. In the S domain, the cysteine residues and the secondary structures of the alpha-helix and beta-sheet were likely critical for the stable folding of the protein structure. The preC domain and C-terminal domain (CTD) of the core protein are highly conserved. And the polymerases HBpol and the HBx were highly variable at the amino acid level.

scholarly journals Fine Mapping of Pre-S Sequence Requirements for Hepatitis B Virus Large Envelope Protein-Mediated Receptor Interaction

2009 ◽  
Vol 84 (4) ◽  
pp. 1989-2000 ◽  
Author(s):  
Andreas Schulze ◽  
Alexa Schieck ◽  
Yi Ni ◽  
Walter Mier ◽  
Stephan Urban
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Inhibitory Activity ◽  
Point Mutations ◽  
Virus Infectivity ◽  
Heparg Cell Line ◽  
B Virus ◽  
Sequence Requirements

ABSTRACT Previous studies showed that the N-terminal 75 amino acids of the pre-S1 domain of the hepatitis B virus (HBV) L protein are essential for HBV and hepatitis delta virus (HDV) infectivity. Consistently, synthetic lipopeptides encompassing this sequence or only parts of it efficiently block HBV and HDV infection, presumably through specific interference with a cellular receptor. Crucial for both virus infectivity and the inhibitory activity of the peptides are N-terminal myristoylation and a highly conserved motif within the N-terminal 48 amino acids. To refine the sequence requirements, we synthesized a series of HBV pre-S1 peptides containing deletions, point mutations, d-amino acid exchanges, or genotype-specific sequence permutations. Using the HepaRG cell line and a genotype D-derived virus, we determined the specific inhibitory activities of the peptides and found that (i) lipopeptides with an artificial consensus sequence inhibit HBV genotype D infection more potently than the corresponding genotype D peptides; (ii) point mutations, d-amino acid exchanges, or deletions introduced into the highly conserved part of the pre-S1 domain result in an almost complete loss of activity; and (iii) the flanking sequences comprising amino acids 2 to 8, 16 to 20, and, to a less pronounced extent, 34 to 48 gradually increase the inhibitory activity, while amino acids 21 to 33 behave indifferently. Taken together, our data suggest that HBV pre-S1-mediated receptor interference and, thus, HBV receptor recognition form a highly specific process. It requires an N-terminal acyl moiety and a highly conserved sequence that is present in primate but not rodent or avian hepadnaviruses, indicating different entry pathways for the different family members.

scholarly journals The Pre-S2 Domain of the Hepatitis B Virus Is Dispensable for Infectivity but Serves a Spacer Function for L-Protein-Connected Virus Assembly

2010 ◽  
Vol 84 (8) ◽  
pp. 3879-3888 ◽  
Author(s):  
Yi Ni ◽  
Jessika Sonnabend ◽  
Stefan Seitz ◽  
Stephan Urban
Keyword(s):  
Amino Acids ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Conformational Changes ◽  
Virus Assembly ◽  
M Protein ◽  
L Protein ◽  
Heparg Cells ◽  
B Virus

ABSTRACT The envelope of the human hepatitis B virus (HBV) contains three membrane proteins (L, M, and S). They accomplish different functions in HBV infectivity and nucleocapsid envelopment. Infectivity determinants have been assigned to the N-terminal part of the pre-S1 domain of the L protein and the antigenic loop of the S domain in the L and/or S protein. Nucleocapsid envelopment requires a C-terminal sequence within pre-S1, including the five N-terminal amino acids of pre-S2 as part of the L protein. However, the role of the M protein and the pre-S2 domain of the L protein are not entirely understood. We addressed this question and analyzed assembly competence and infectivity of viruses that lack the M protein and, at the same time, carry alterations in the pre-S2 domain of L. These include deletions, in part frameshift mutations and a randomization of virtually the entire pre-S2 sequence. We found that the M protein is dispensable for HBV in vitro infectivity. Viruses that lack the M protein and contain a mostly randomized pre-S2 sequence assemble properly and are infectious in HepaRG cells and primary human hepatocytes. While deletions of 20 amino acids in the pre-S2 domain of L protein allowed the production of infectious virions, more extended deletions interfered with assembly. This indicates that the pre-S2 domain of the L protein serves an important role for virus assembly, presumably as a spacer that supports conformational changes of L protein but does not participate as part of the M protein or as a subdomain of the L protein in virus entry.

scholarly journals The Variability of Amino Acid Sequences in Hepatitis B Virus

2019 ◽  
Vol 34 (1) ◽  
pp. 42-49 ◽  
Author(s):  
Jianhao Cao ◽  
Shuhong Luo ◽  
Yuanyan Xiong
Keyword(s):  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Amino Acid Sequences ◽  
B Virus

scholarly journals Role of the Pre-S2 Domain of the Large Envelope Protein in Hepatitis B Virus Assembly and Infectivity

1998 ◽  
Vol 72 (7) ◽  
pp. 5573-5578 ◽  
Author(s):  
J. Le Seyec ◽  
P. Chouteau ◽  
I. Cannie ◽  
C. Guguen-Guillouzo ◽  
P. Gripon
Keyword(s):  
Amino Acids ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Assembly ◽  
Critical Role ◽  
Surface Protein ◽  
Virion Release ◽  
B Virus ◽  
Viral Maturation

ABSTRACT Among the three viral proteins present in the hepatitis B virus (HBV) envelope, both the small and large polypeptides, but not the middle polypeptide, are necessary for the production of complete viral particles. Whereas it has been established that the C-terminal extremity of the pre-S1 region is required for HBV morphogenesis, whether the pre-S2 region of the large surface protein plays a critical role remains questionable. In the present study, we have analyzed the role of the large-polypeptide pre-S2 region in viral maturation and infectivity. For this purpose, mutants bearing contiguous deletions covering the entire pre-S2 domain were generated. First, the efficient expression of all the mutant large envelope proteins was verified and their ability to substitute for the wild-type form in virion secretion was tested. We found that distinct deletions covering the domain between amino acids 114 and 163 still allowed virion production. In contrast, the polypeptide lacking the first 5 amino acids of pre-S2 (amino acids 109 to 113) was unable to support viral secretion. This result shows that the domain of the large surface protein, required for this process, must be extended to the N-terminal extremity of pre-S2. We then demonstrated that all the mutants competent for virion release were able to infect normal human hepatocytes in primary culture. Taken together, these results indicate that only 10% of the large-protein pre-S2 region at its N-terminal extremity is essential for virion export and that the remaining part, dispensable for viral secretion, is also dispensable for infectivity.

scholarly journals Early Evolution of Hepatitis B Virus Quasispecies During IFN-α Treatment

2014 ◽  
Vol 3 (4) ◽  
pp. 152-160
Author(s):  
Yu-lian Ren ◽  
Yao Xie
Keyword(s):  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virological Response ◽  
Complete Genome ◽  
Early Stage ◽  
Amino Acid Level ◽  
B Virus ◽  
Amino Acid Levels ◽  
Quasispecies Diversity

Abstract Objective To investigate the dynamic change of hepatitis B virus quasispecies within complete genome during the early stage of IFN-α treatment and its impact on virological response. Methods Sixteen patients with chronic hepatitis B receiving IFN-α treatment were investigated. HBV DNA was extracted from serum sample at baseline and week 12. The complete genome of HBV was amplified, then cloned and sequenced. The quasispecies heterogeneity of HBV complete genome was depicted at baseline and week 12. Results The quasispecies heterogeneity of the genome except for C-ORF were comparable in three groups at baseline and week 12. The quasispecies diversity at amino acid levels of responders within C-ORF were higher than that of non-responders at baseline. The quasispecies diversity within the C-ORF of partial responders was reduced in the early stage of IFN-α treatment. Furthermore, the mean genetic distance at amino acid levels of partial responders was significantly higher than that of the non-responders at week 12. The evolutionary rate was not different between non-responders and partial responders. Conclusions In the immune clearance phase, the patients who had greater viral quasispecies diversity within C-ORF at amino acid level had more chance to obtain the early virological response during IFN-α treatment.

scholarly journals Structure of hepatitis B virus core and e-antigen. A single precore amino acid prevents nucleocapsid assembly.

1993 ◽  
Vol 268 (2) ◽  
pp. 1332-1337
Author(s):  
F. Schödel ◽  
D. Peterson ◽  
J. Zheng ◽  
J.E. Jones ◽  
J.L. Hughes ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Core ◽  
B Virus ◽  
Antigen A

scholarly journals A Divergent Hepatitis D-Like Agent in Birds

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 720 ◽  
Author(s):  
Michelle Wille ◽  
Hans Netter ◽  
Margaret Littlejohn ◽  
Lilly Yuen ◽  
Mang Shi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hepatitis B Virus ◽  
Sequence Analysis ◽  
Hepatitis B ◽  
Hepatitis Delta Virus ◽  
Amino Acid Similarity ◽  
Hepatitis D ◽  
Delta Antigen ◽  
B Virus ◽  
Delta Virus

Hepatitis delta virus (HDV) is currently only found in humans and is a satellite virus that depends on hepatitis B virus (HBV) envelope proteins for assembly, release, and entry. Using meta-transcriptomics, we identified the genome of a novel HDV-like agent in ducks. Sequence analysis revealed secondary structures that were shared with HDV, including self-complementarity and ribozyme features. The predicted viral protein shares 32% amino acid similarity to the small delta antigen of HDV and comprises a divergent phylogenetic lineage. The discovery of an avian HDV-like agent has important implications for the understanding of the origins of HDV and sub-viral agents.

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