A Unique Amino Acid Substitution, L215Q, in the Hepatitis B Virus Small Envelope Protein of a Genotype F Isolate That Inhibits Secretion of Hepatitis B Virus Subviral Particles

Intervirology ◽  
2008 ◽  
Vol 51 (2) ◽  
pp. 81-86 ◽  
Author(s):  
Natalia M. Araujo ◽  
Carlos O.A. Vianna ◽  
Caroline C. Soares ◽  
Selma A. Gomes
Keyword(s):  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Amino Acid Substitution ◽  
Envelope Protein ◽  
Unique Amino Acid Substitution ◽  
B Virus ◽  
Unique Amino Acid ◽  
Genotype F ◽  
Subviral Particles

A unique amino acid substitution, T126I, in human genotype C of hepatitis B virus S gene and its possible influence on antigenic structural change

Gene ◽  
2006 ◽  
Vol 383 ◽  
pp. 43-51 ◽  
Author(s):  
Fengrong Ren ◽  
Asahito Tsubota ◽  
Takatsugu Hirokawa ◽  
Hiromitsu Kumada ◽  
Ziheng Yang ◽  
...  
Keyword(s):  
Structural Change ◽  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Amino Acid Substitution ◽  
Unique Amino Acid Substitution ◽  
S Gene ◽  
B Virus ◽  
Genotype C ◽  
Unique Amino Acid

scholarly journals A Putative Amphipathic Alpha Helix in Hepatitis B Virus Small Envelope Protein Plays a Critical Role in the Morphogenesis of Subviral Particles

2021 ◽  
Vol 95 (8) ◽  
Author(s):  
Sisi Yang ◽  
Zhongliang Shen ◽  
Yaoyue Kang ◽  
Liren Sun ◽  
Usha Viswanathan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Envelope Protein ◽  
Alpha Helix ◽  
Hbv Infection ◽  
20S Proteasome ◽  
S Protein ◽  
B Virus ◽  
Amphipathic Alpha Helix ◽  
Subviral Particles

ABSTRACT Hepatitis B virus (HBV) small (S) envelope protein has the intrinsic ability to direct the formation of small spherical subviral particles (SVPs) in eukaryotic cells. However, the molecular mechanism underlying the morphogenesis of SVPs from the monomeric S protein initially synthesized at the endoplasmic reticulum (ER) membrane remains largely elusive. Structure prediction and extensive mutagenesis analysis suggested that the amino acid residues spanning W156 to R169 of S protein form an amphipathic alpha helix and play essential roles in SVP production and S protein metabolic stability. Further biochemical analyses showed that the putative amphipathic alpha helix was not required for the disulfide-linked S protein oligomerization but was essential for SVP morphogenesis. Pharmacological disruption of vesicle trafficking between the ER and Golgi complex in SVP-producing cells supported the hypothesis that S protein-directed SVP morphogenesis takes place at the ER-Golgi intermediate compartment (ERGIC). Moreover, it was demonstrated that S protein is degraded in hepatocytes via a 20S proteasome-dependent but ubiquitination-independent nonclassic ER-associated degradation pathway. Taken together, the results reported here favor a model in which the amphipathic alpha helix at the antigenic loop of S protein attaches to the lumen leaflet to facilitate SVP budding from the ERGIC, whereas the failure of the budding process may result in S protein degradation by 20S proteasome in a ubiquitination-independent manner. IMPORTANCE SVPs are the predominant viral product produced by HBV-infected hepatocytes. Their levels exceed those of virion particles by 10,000- to 100,000-fold in the blood of HBV-infected individuals. The high levels of SVPs, or HBV surface antigen (HBsAg), in the circulation induce immune tolerance and contribute to the establishment of persistent HBV infection. The loss of HBsAg, often accompanied by the appearance of anti-HBsAg antibodies, is the hallmark of durable immune control of HBV infection. Therapeutic induction of HBsAg loss is thus considered to be essential for the restoration of the host antiviral immune response and functional cure of chronic hepatitis B. Our findings on the mechanism of SVP morphogenesis and S protein metabolism will facilitate the rational discovery and development of antiviral drugs to achieve this therapeutic goal.

scholarly journals Emergence of a Novel Lamivudine-Resistant Hepatitis B Virus Variant with a Substitution Outside the YMDD Motif

2006 ◽  
Vol 50 (11) ◽  
pp. 3867-3874 ◽  
Author(s):  
Hiromi Yatsuji ◽  
Chiemi Noguchi ◽  
Nobuhiko Hiraga ◽  
Nami Mori ◽  
Masataka Tsuge ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mutant Strain ◽  
Amino Acid Substitution ◽  
Nucleotide Substitution ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Mutant Strains ◽  
Ymdd Motif

ABSTRACT Lamivudine is a major drug approved for treatment of chronic hepatitis B virus (HBV) infection. Emergence of drug-resistant mutants with amino acid substitutions in the YMDD motif is a well-documented problem during long-term lamivudine therapy. Here we report a novel lamivudine-resistant strain of HBV with an intact YMDD motif, which included an amino acid substitution, rtA181T, in the reverse transcriptase (RT) domain of HBV polymerase. The substitution also induced a unique amino acid substitution (W172L) in the overlapping hepatitis B surface (HBs) protein. The YMDD mutant strains were not detected even by using the sensitive peptide nucleic acid-mediated PCR clamping method. The detected nucleotide substitution was accompanied by the emergence of an additional nucleotide substitution that induced amino acid change (S331C) in the spacer domain. The rtA181T mutant strain displayed a threefold decrease in susceptibility to lamivudine in in vitro experiments in comparison with the wild type. In vivo analysis using human hepatocyte-chimeric mice confirmed the resistance of this mutant strain to lamivudine. We developed a method to detect this novel rtA181T mutation and a previously reported rtA181T mutation with the HBs stop codon using restriction fragment length polymorphism PCR and identified one patient with the latter pattern among 40 patients with lamivudine resistance. In conclusion, although the incidence is not high, we have to be careful regarding the emergence of lamivudine-resistant mutant strains with intact YMDD motif.

Preclinical studies on Myrcludex B, a novel Hepatitis B virus (HBV)-envelope protein derived entry inhibitor

2010 ◽  
Vol 48 (01) ◽  
Author(s):  
A Schulze ◽  
A Schieck ◽  
C Gähler ◽  
A Meier ◽  
T Müller ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Envelope Protein ◽  
Entry Inhibitor ◽  
Preclinical Studies ◽  
B Virus

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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