scholarly journals Myristoylated PreS1-domain of the hepatitis B virus L-protein mediates specific binding to differentiated hepatocytes

Hepatology ◽  
2013 ◽  
Vol 58 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Anja Meier ◽  
Stefan Mehrle ◽  
Thomas S. Weiss ◽  
Walter Mier ◽  
Stephan Urban
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Specific Binding ◽  
L Protein ◽  
B Virus ◽  
Pres1 Domain

scholarly journals Hepatitis B Virus Large Envelope Protein Interacts with γ2-Adaptin, a Clathrin Adaptor-Related Protein

2001 ◽  
Vol 75 (11) ◽  
pp. 5343-5351 ◽  
Author(s):  
Cora Hartmann-Stühler ◽  
Reinhild Prange
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Envelope Protein ◽  
Specific Binding ◽  
Dna Amplification ◽  
Host Protein ◽  
Physical Interaction ◽  
L Protein ◽  
B Virus ◽  
Clathrin Adaptor

ABSTRACT For the outcome of a hepatitis B virus (HBV) infection, the viral L envelope protein with its pre-S domain performs pivotal functions by mediating attachment of HBV to liver cells, envelopment of viral capsids, release of (sub)viral particles, regulation of supercoiled DNA amplification, and transcriptional transactivation. To assess its multiple functions and host-protein assistance involved, we initiated a two-hybrid screen using the L-specific pre-S1 domain as bait. With this approach, we have identified γ2-adaptin, a putative member of the clathrin adaptor proteins responsible for protein sorting and trafficking, as a specific binding partner of L protein. Evidence for a physical interaction between L protein and γ2-adaptin was also demonstrated by affinity chromatography and coimmunoprecipitation, and the binding sites were mapped to the L-specific pre-S1 domain and the γ2-adaptin-specific ear domain. The specificity of the interaction was further sustained by the failure of γ1-adaptin, a closely related γ2-adaptin homologue, to associate with L protein. Analysis of an L mutant protein indicates that the L–γ2-adaptin interaction strictly depends on the pre-S1 domain of transmembrane L protein oriented to the cytosol and thus appears to occur in the cytosolic environment. Interestingly, coexpression of the two interacting partners in transfected cells resulted in recruitment of γ2-adaptin by L protein onto cis-Golgi-like structures, strongly indicating that the association is physiologically relevant. Together, the results suggest a role for γ2-adaptin in L-mediated processes of viral biogenesis and/or pathogenesis, such as facilitating and guiding HBV assembly.

Epitope mapping of the PreS1 domain of the hepatitis B virus large surface protein

Virology ◽  
1990 ◽  
Vol 176 (2) ◽  
pp. 620-624 ◽  
Author(s):  
Kazuyuki Kuroki ◽  
Marco Floreani ◽  
Larry T. Mimms ◽  
Don Ganem
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Epitope Mapping ◽  
Surface Protein ◽  
B Virus ◽  
Pres1 Domain

scholarly journals Envelope Protein-Mediated Down-Regulation of Hepatitis B Virus Receptor in Infected Hepatocytes

2001 ◽  
Vol 75 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Klaus M. Breiner ◽  
Stephan Urban ◽  
Bärbel Glass ◽  
Heinz Schaller
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Envelope Protein ◽  
Recombinant Adenovirus ◽  
Down Regulation ◽  
Virus Receptor ◽  
L Protein ◽  
Duck Hepatitis ◽  
B Virus ◽  
Golgi Compartment

ABSTRACT Entry of duck hepatitis B virus (DHBV) is initiated by specific interaction of its large envelope protein (L) with a cellular entry receptor, recently identified as carboxypeptidase D (CPD; historically gp180). In this report, we present evidence demonstrating that this receptor is down-regulated as a result of DHBV infection: (i) receptor levels determined by Western blot were much reduced in DHBV-infected duck livers and undetectable by immunostaining in infected cultured hepatocytes; (ii) results from metabolic labeling experiments indicate enhanced receptor protein turnover; (iii) the kinetics of receptor loss from newly infected cells correlated with the accumulation of newly synthesized viral protein; (iv) expression of DHBV L protein, transduced from a recombinant adenovirus, was sufficient to eliminate gp180/CPD from the Golgi compartment, its normal predominant location; (v) gp180/CPD remained absent from the Golgi compartment in infected hepatocytes, even after overexpression from a recombinant adenovirus, while residual amounts subsequently became detectable in a perinuclear compartment, containing DHBV L protein; (vi) expression of DHBV L protein in a HepG2 cell line, stably expressing gp180/CPD, leads to incomplete receptor maturation and induces its degradation. Taken together, these data are consistent with a model in which the virus receptor interacts early in the biosynthetic pathway with the viral L protein, leading to its retention in a pre-Golgi compartment and to subsequent degradation, thus preventing receptor interference with the export of DHBV via the secretory pathway which it shares with its receptor. Accordingly, and analogously with receptor down-regulation in retroviral systems, DHBV receptor down-modulation may account for the much-reduced efficiency of DHBV superinfection of preinfected hepatocytes.

scholarly journals The preS1 domain of hepatitis B virus and IgA cross-react in their binding to the hepatocyte surface

1992 ◽  
Vol 73 (8) ◽  
pp. 2041-2045 ◽  
Author(s):  
P. Pontisso ◽  
M. G. Ruvoletto ◽  
C. Tiribelli ◽  
W. H. Gerlich ◽  
A. Ruol ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
B Virus ◽  
Pres1 Domain

scholarly journals Infection Process of the Hepatitis B Virus Depends on the Presence of a Defined Sequence in the Pre-S1 Domain

1999 ◽  
Vol 73 (3) ◽  
pp. 2052-2057 ◽  
Author(s):  
J. Le Seyec ◽  
P. Chouteau ◽  
I. Cannie ◽  
C. Guguen-Guillouzo ◽  
P. Gripon
Keyword(s):  
Amino Acids ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Protein ◽  
Infection Process ◽  
Viral Infectivity ◽  
Mutant Proteins ◽  
L Protein ◽  
Virion Release ◽  
B Virus

ABSTRACT During the life cycle of hepatitis B virus (HBV), the large envelope protein (L) plays a pivotal role. Indeed, this polypeptide is essential for viral assembly and probably for the infection process. By performing mutagenesis experiments, we have previously excluded a putative involvement of the pre-S2 domain of the L protein in viral infectivity. In the present study, we have evaluated the role of the pre-S1 region in HBV infection. For this purpose, 21 mutants of the L protein were created. The entire pre-S1 domain was covered by contiguous deletions of 5 amino acids. First, after transfection into HepG2 cells, the efficient expression of both glycosylated and unglycosylated L mutant proteins was verified. The secretion rate of envelope proteins was modified positively or negatively by deletions, indicating that the pre-S1 domain contains several regulating sequences able to influence the surface protein secretion. The ability of mutant proteins to support the production of virions was then studied. Only the four C-terminal deletions, covering the 17 amino acids suspected to interact with the cytoplasmic nucleocapsids, inhibited virion release. Finally, the presence of the modified pre-S1 domain at the external side of all secreted virions was confirmed, and their infectivity was assayed on normal human hepatocytes in primary culture. Only a short sequence including amino acids 78 to 87 tolerates internal deletions without affecting viral infectivity. These results confirm the involvement of the L protein in the infection step and demonstrate that the sequence between amino acids 3 and 77 is involved in this process.

scholarly journals Drastic Reduction in the Production of Subviral Particles Does Not Impair Hepatitis B Virus Virion Secretion

2009 ◽  
Vol 83 (21) ◽  
pp. 11152-11165 ◽  
Author(s):  
Tamako Garcia ◽  
Jisu Li ◽  
Camille Sureau ◽  
Kiyoaki Ito ◽  
Yanli Qin ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
M Protein ◽  
Dependent Manner ◽  
Drastic Reduction ◽  
S Protein ◽  
L Protein ◽  
B Virus ◽  
S Proteins ◽  
Subviral Particles

ABSTRACT Hepatitis B virus (HBV) contains three coterminal envelope proteins on the virion surface: large (L), middle (M), and small (S). The M and S proteins are also secreted as empty “subviral particles,” which exceed virions by at least 1,000-fold. The S protein serves as the morphogenic factor for both types of particles, while the L protein is required only for virion formation. We found that cotransfecting replication constructs with a small dose of the expression construct for the missing L, M, and S proteins reconstituted efficient virion secretion but only 5 to 10% of subviral particles. The L protein inhibited secretion of subviral particles in a dose-dependent manner, whereas a too-high or too-low L/S protein ratio inhibited virion secretion. Consistent with the results of cotransfection experiments, a point mutation at the −3 position of the S gene AUG codon reduced HBsAg secretion by 60 to 70% but maintained efficient virion secretion. Surprisingly, ablating M protein expression reduced virion secretion but markedly increased the maturity of virion-associated genomes, which could be reversed by providing in trans both L and M proteins but not just M protein. M protein stability was dependent on the coexpression of S protein. Our findings suggest that efficient HBV virion secretion could be maintained despite drastic reduction in subviral particle production, which supports the recent demonstration of separate secretion pathways adopted by the two types of particles. The M protein appears to facilitate core particle envelopment, thus shortening the window of plus strand DNA elongation.

Liver cell-specific peptides derived from the preS1 domain of human hepatitis B virus

2014 ◽  
Vol 201 ◽  
pp. 20-23 ◽  
Author(s):  
Jeong-Hun Kang ◽  
Riki Toita ◽  
Daisuke Asai ◽  
Tetsuji Yamaoka ◽  
Masaharu Murata
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Liver Cell ◽  
Human Hepatitis ◽  
B Virus ◽  
Pres1 Domain

scholarly journals A Short N-Proximal Region in the Large Envelope Protein Harbors a Determinant That Contributes to the Species Specificity of Human Hepatitis B Virus

2001 ◽  
Vol 75 (23) ◽  
pp. 11565-11572 ◽  
Author(s):  
P. Chouteau ◽  
J. Le Seyec ◽  
I. Cannie ◽  
M. Nassal ◽  
C. Guguen-Guillouzo ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Host Range ◽  
Envelope Protein ◽  
Envelope Proteins ◽  
Species Specificity ◽  
Wild Type ◽  
Woolly Monkey ◽  
L Protein ◽  
B Virus

ABSTRACT Infection by hepatitis B virus (HBV) is mainly restricted to humans. This species specificity is likely determined at the early phase of the viral life cycle. Since the envelope proteins are the first viral factors to interact with the cell, they represent attractive candidates for controlling the HBV host range. To investigate this assumption, we took advantage of the recent discovery of a second virus belonging to the primateOrthohepadnavirus genus, the woolly monkey HBV (WMHBV). A recombinant plasmid was constructed for the expression of all WMHBV envelope proteins. In additional constructs, N-terminal sequences of the WMHBV large envelope protein were substituted for their homologous HBV counterparts. All wild-type and chimeric WMHBV surface proteins were properly synthesized by transfected human hepatoma cells, and they were competent to replace the original HBV proteins for the production of complete viral particles. The resulting pseudotyped virions were evaluated for their infectious capacity on human hepatocytes in primary culture. Virions pseudotyped with wild-type WMHBV envelope proteins showed a significant loss of infectivity. By contrast, infectivity was completely restored when the first 30 residues of the large protein originated from HBV. Analysis of smaller substitutions within this domain limited the most important region to a stretch of only nine amino acids. Reciprocally, replacement of this motif by WMHBV residues in the context of the HBV L protein significantly reduced infectivity of HBV. Hence this short region of the L protein contributes to the host range of HBV.

Endonexin II, Present on Human Liver Plasma Membranes, Is a Specific Binding Protein of Small Hepatitis B Virus (HBV) Envelope Protein

Virology ◽  
1993 ◽  
Vol 197 (2) ◽  
pp. 549-557 ◽  
Author(s):  
Kurt Hertogs ◽  
William P.J. Leenders ◽  
Erick Depla ◽  
Wieke C.C. De Bruin ◽  
Lydie Meheus ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Envelope Protein ◽  
Human Liver ◽  
Plasma Membranes ◽  
Specific Binding ◽  
Binding Protein ◽  
Liver Plasma Membranes ◽  
B Virus ◽  
Specific Binding Protein

scholarly journals Normal phosphorylation of duck hepatitis B virus L protein is dispensable for infectivity.

1998 ◽  
Vol 79 (11) ◽  
pp. 2743-2751 ◽  
Author(s):  
E V Grgacic ◽  
E V Gazina ◽  
B Lin ◽  
D A Anderson ◽  
M J Snooks
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Duck Hepatitis B Virus ◽  
L Protein ◽  
Duck Hepatitis ◽  
B Virus
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