Large surface proteins of hepatitis B virus containing the pre-s sequence

Heermann, Klaus-Hinrich; Goldmann, Udo; Schwartz, W; Seyffarth, T; Baumgarten, H.; Gerlich, Wolfram H.

doi:10.1128/jvi.52.2.396-402.1984

Cited by 766 publications

(403 citation statements)

References 29 publications

Supporting

Mentioning

386

Contrasting

Unclassified

Order By: Relevance

“…HBV is an enveloped virus containing a small genome of 3.2 kb of partially double-stranded DNA encoding four overlapping reading frames. The HBV envelope consists of the small (S), middle (M), and large (L) envelope proteins, which are multiple transmembrane spanners sharing the same C-terminal domain corresponding to the S protein but differing at their N-terminal domains ( Figure 1A) (Heermann et al, 1984;Seeger et al, 2007). HDV is a small satellite RNA virus of HBV carrying all three HBV envelope proteins and can only propagate when coexisting with HBV.…”

Section: Introductionmentioning

confidence: 99%

Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Yan

Zhong

et al. 2012

eLife

1,791

1,885

View full text Add to dashboard Cite

Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.DOI: http://dx.doi.org/10.7554/eLife.00049.001

show abstract

Section: Introductionmentioning

confidence: 99%

Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Yan

Zhong

et al. 2012

eLife

1,791

1,885

View full text Add to dashboard Cite

show abstract

“…When the effects of different inhibitors were monitored, the cells were incubated with medium containing 400 M buthionine sulfoximine (BSO), 50 nM bafilomycin A (Baf), 50 mM NH 4 Cl or 100 M E64d. The drugs were added either after removal of the HBV inoculum (BSO) or 24 h later (BSO, Baf, NH 4 Cl, and E64d) and were maintained for 24 h. Infected cells were harvested 14 days p.i., and the encapsidated viral DNA was quantified by real-time PCR. All infection experiments were performed with duplicate samples and repeated at least three times.…”

Section: Methodsmentioning

confidence: 99%

“…The nucleocapsid surrounds the relaxed circular, partially double-stranded DNA genome, to which the viral polymerase is covalently attached (3). Apart from the crucial roles played in virus morphogenesis and infection, the envelope proteins bear the intriguing property to self-assemble into spherical and filamentous subviral particles (SVP), which are released from cells in vast excess over virions, accounting for more than 90% of the total particles in the serum of infected patients (4).…”

mentioning

confidence: 99%

Regulation of Hepatitis B Virus Infection by Rab5, Rab7, and the Endolysosomal Compartment

Macovei

Petrareanu

Lazar

et al. 2013

J Virol

100

View full text Add to dashboard Cite

Despite important progress toward deciphering human hepatitis B virus (HBV) entry into host cells, many aspects of the early steps of the life cycle remained completely obscure. Following endocytosis, HBV must travel through the complex network of the endocytic pathway to reach the cell nucleus and initiate replication. In addition to guiding the viral particles to the replication site, the endosomal vesicles may play a crucial role in infection, providing the appropriate environment for virus uncoating and nucleocapsid release. In this work, we investigated the trafficking of HBV particles internalized in permissive cells. Expression of key Rab proteins, involved in specific pathways leading to different intracellular locations, was modulated in HepaRG cells, using a stable and inducible short hairpin RNA (shRNA) expression system. The trafficking properties of the newly developed cells were demonstrated by confocal microscopy and flow cytometry using specific markers. The results showed that HBV infection strongly depends on Rab5 and Rab7 expression, indicating that HBV transport from early to mature endosomes is required for a step in the viral life cycle. This may involve reduction of disulfide bond-linked envelope proteins, as alteration of the redox potential of the endocytic pathway resulted in inhibition of infection. Subcellular fractionation of HBV-infected cells showed that viral particles are further transported to lysosomes. Intriguingly, infection was not dependent on the lysosomal activity, suggesting that trafficking to this compartment is a "dead-end" route. Together, these data add to our understanding of the HBV-host cell interactions controlling the early stages of infection. C hronic hepatitis B virus (HBV) infections can lead to lifethreatening liver diseases, such as cirrhosis and hepatocellular carcinoma, the third cause of cancer deaths worldwide (1). Infectious viral particles consist of an icosahedral nucleocapsid made of the core protein and a lipid bilayer embedding the small (S), middle (M), and large (L) envelope proteins (2). The nucleocapsid surrounds the relaxed circular, partially double-stranded DNA genome, to which the viral polymerase is covalently attached (3). Apart from the crucial roles played in virus morphogenesis and infection, the envelope proteins bear the intriguing property to self-assemble into spherical and filamentous subviral particles (SVP), which are released from cells in vast excess over virions, accounting for more than 90% of the total particles in the serum of infected patients (4).Studies regarding the early events of the HBV life cycle have been particularly problematic, as human primary hepatocytes, the physiological host, are difficult to procure and maintain in tissue culture and are refractory to genetic manipulation. The development of alternative infectivity models for HBV, represented by proliferating liver-derived cell lines able to differentiate and support HBV infection in vitro, has considerably overcome many of these drawbacks (5-7). Moreo...

show abstract

“…One HBsAg preparation (pHBs) containing HBs, preS1 and preS2 sequences was purified from the plasma of patients with chronic HBV infection of adw subtype, that is known to be most common in Western Europe [15]. A recombinant HBsAg preparation (rHBs) derived from yeast cultures containing exclusively HBs was kindly provided by B. Hoffstedt (MSD, Sharp & Dohme, München, Germany).…”

Section: Hbv Antigensmentioning

confidence: 99%

Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection

Böcher

Herzog-Hauff

Herr

et al. 1996

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYAntibodies directed to the HBs antigen indicate viral clearance and the development of life-long immunity in patients that recovered from HBV infection. In HBs antigen vaccine recipients anti-HBs antibodies provide protective immunity. However, little is known about the regulation of this HBsspecific antibody response. The existence of anti-HBs-secreting B cells was demonstrated using the highly sensitive ELISPOT technique compared with conventional ELISA in serum and cell culture supernatants. In the peripheral blood of patients with acute self-limited hepatitis B, HBs-specific B cells were demonstrated with a high frequency despite undetectable anti-HBs serum antibodies. HBVimmunized patients that had recovered from infection and vaccine recipients had significantly lower frequencies, whereas chronic HBV carriers and negative controls showed no anti-HBs-secreting B cells. Coculture experiments of isolated B and T cells revealed that the anti-HBs antibody response was restricted to the presence of T helper cells, but not to identical HLA class II molecules. Allogeneic T cells derived from vaccine recipients or chronic HBV carriers stimulated the HBs-specific B cell response in HBs vaccine recipients. Otherwise, isolated T helper cells could never provide sufficient help to induce the HBs-specific B cell response in chronic HBV carriers. Furthermore, peripheral blood mononuclear cells (PBMC) of six out of 10 vaccine recipients, one out of five HBV-immunized patients, but of no chronic HBV carrier showed a proliferative response to different HBs antigen preparations. This study demonstrated a high frequency of circulating anti-HBs-producing B cells in the early phase of acute HBV infection, but a lower frequency of HBs-specific B cells years after resolution of HBV infection. In chronic HBV carriers, however, deficient HBs-specific T and B cell responses were observed.

show abstract

Large surface proteins of hepatitis B virus containing the pre-s sequence

Cited by 766 publications

References 29 publications

Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

Regulation of Hepatitis B Virus Infection by Rab5, Rab7, and the Endolysosomal Compartment

Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection

Contact Info

Product

Resources

About