Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endonexin II present on the surface of human hepatocytes has recently been identified as a hepatitis B virus surface antigen (HBsAg) binding protein. A full-length cDNA clone encoding human endonexin II was isolated from a human liver cDNA library and was placed under the control of the polyhedrin promoter of Autographa californica nuclear polyhedrosis virus (AcNPV). Infection of Spodoptera frugiperda cells with recombinant virus resulted in the production of high amounts of recombinant protein. This protein has the same molecular weight and iso-electric point as native human endonexin II. It can be easily purified by methods analogous to those described for the native protein. Moreover, the recombinant product binds very efficiently to hepatitis B surface proteins (HBsAg) in a similar fashion as native human endonexin II.
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PMID:Cloning and production of functional active recombinant hepatitis B virus surface antigen binding protein. 799 73

Annexin V and apolipoprotein H, reported to bind hepatitis B surface antigen (HBsAg) and presumed to react specifically with the HBsAg S protein and to play an important role in initiation of infection by hepatitis B virus, did not bind to delipidated HBsAg (dlHBsAg). Binding activity was restored by adding lipids to dlHBsAg. These results are consistent with the established affinity of annexin V and apolipoprotein H for lipids.
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PMID:The putative cell receptors for hepatitis B virus (HBV), annexin V, and apolipoprotein H, bind to lipid components of HBV. 809 82

In a previous study, we have identified endonexin II (E-II) on human liver plasma membranes as a specific, Ca(2+)-dependent, small hepatitis B surface antigen (HBsAg)-binding protein. In this article, we describe the spontaneous development of anti-HBs antibodies in rabbits immunized with native or recombinant human liver E-II and in chickens immunized with the F(ab')2 fragment of rabbit anti-human liver E-II immunoglobulin G. Anti-HBs activity was not observed in rabbits immunized with rat liver E-II. Cross-reactivity of anti-E-II antibodies to HBsAg epitopes was excluded, since anti-HBs and anti-E-II activities can be separated by E-II affinity chromatography. The existence of an anti-idiotypic antibody is further demonstrated by competitive binding of human liver E-II and this antibody (Ab2) to small HBsAg, suggesting that Ab2 mimics a specific E-II epitope that interacts with small HBsAg. In addition, it was demonstrated that anti-HBs antibodies developed in rabbits after immunization with intact human liver E-II or in chickens after immunization with F(ab')2 fragments of rabbit anti-human liver E-II immunoglobulin G recognize the same epitopes on small HBsAg. These findings strongly indicate that human liver E-II is a very specific small HBsAg-binding protein and support the assumption that human liver E-II is the hepatitis B virus receptor protein.
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PMID:Spontaneous development of anti-hepatitis B virus envelope (anti-idiotypic) antibodies in animals immunized with human liver endonexin II or with the F(ab')2 fragment of anti-human liver endonexin II immunoglobulin G: evidence for a receptor-ligand-like relationship between small hepatitis B surface antigen and endonexin II. 810 14

Recently we identified human liver endonexin II (EII) as a specific hepatitis B surface antigen (HBsAg) binding protein. To investigate whether EII is also able to interact with the HBsAg envelope of the hepatitis delta virus (H delta V), immunoprecipitation experiments were performed. H delta V particles could be co-precipitated by polyclonal rabbit anti-EII, but not by rabbit anti-glutathiontransferase (GST pi) antibodies from an H delta V-enriched fraction containing EII or GST pi. These findings suggest that H delta V particles were co-precipitated by anti-EII as a consequence of the binding between HBsAg present in the H delta V envelope and EII. Furthermore, binding of H delta V particles to human hepatocytes could be inhibited by incubation of the liver cells with rabbit anti-EII IgG or the H delta V particles with anti-idiotypic (anti-HBsAg) antibodies, developed spontaneously in rabbits immunized with EII. These findings support the assumption that small HBsAg present in the H delta V envelope is important for the attachment to the hepatocytes and that EII plays an important role in this process.
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PMID:Hepatitis delta virus attaches to human hepatocytes via human liver endonexin II, a specific HBsAg binding protein. 879 May 57

Previously, we identified human liver endonexin II (EII) present on human hepatocyte plasma membrane as a specific hepatitis B surface antigen (HBsAg) binding protein. We also showed the spontaneous development of anti-idiotypic (anti-HBsAg) antibodies in rabbits immunized with EII and in chicken immunized with the F(ab')2 fragment of rabbit anti-EII IgG. These findings suggest the existence of a receptor-ligand relationship between EII and HBsAg. In the present study, we demonstrate that small HBsAg conjugated to 10 nm colloidal gold also binds specifically to human hepatocytes. Invagination of the coated pit region at the HBsAg binding sites on the human hepatocyte plasma membrane results in the internalization of the HBsAg-gold particles. The binding and consequently the internalization of HBsAg is inhibited by anti-EII or anti-idiotypic (anti-HBsAg) antibodies. These findings indicate that EII is directly involved in the binding and uptake of hepatitis B envelope proteins.
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PMID:Hepatitis B virus: specific binding and internalization of small HBsAg by human hepatocytes. 904 56

Hepatitis B virus (HBV) infection is still a major public health problem worldwide. Although much information about the molecular biology of HBV has been gained in the last decades, little is known about the mechanism of attachment and penetration of the HBV particle into human hepatocytes. The HBV envelope proteins are important for the interaction between the HBV particle and the hepatocyte plasma membrane. Although initially it was suggested that the preS2 domain could act, via polymerized human serum albumin, as an attachment site to human hepatocytes, in recent years other observations showed that the preS1 domain is probably the most important attachment site to human hepatocytes. However, controversial findings on cellular proteins for binding to the preS1 domain has been described, namely the IgA-, the IL6-, the asialoglycoprotein receptor and GAPD. Although the preS1 attachment site may be important, apo H has been shown to bind specifically to small HBsAg. Recently, we have identified human liver Annexin V as a specific small HBsAg-binding protein. In a preliminary report, the direct involvement of human Annexin V in the initial step of HBV infection has been demonstrated. A rat hepatoma cell line, which does not express human Annexin V and which is not infectable by HBV, gained the ability to become infected by HBV after transfection with human Annexin V. This result may facilitate the progress of HBV receptor research and elucidate the molecular mechanism of the initial step of HBV infection.
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PMID:Organ and species specificity of hepatitis B virus (HBV) infection: a review of literature with a special reference to preferential attachment of HBV to human hepatocytes. 918 23

Previously, we have found that human liver annexin V (hA-V; in earlier reports referred as Endonexin II) is a specific hepatitis B surface antigen (HBsAg) binding protein. In this study, we demonstrate that transfection of rat hepatoma FTO 2B cells, a cell line that is not infectable by hepatitis B virus (HBV) and does not express hA-V, with a construct containing the hA-V gene, resulted in hA-V expressing cells susceptible to HBV infection. After in vitro infection, transfected FTO cells (assigned as FTO 9.1 cells) expressing hA-V in cultures were shown to contain HBV-precore/core, X mRNAs, and covalently closed circular (ccc) DNA as detected by polymerase chain reaction (PCR). The presence of HBV ccc and replicative intermediate DNA was also demonstrated by Southern blot hybridization assay. HBV DNA secreted in the culture medium was also evident as determined by quantitative branched DNA (bDNA) assay. HBsAg and hepatitis B core antigen (HBcAg) could also be detected by an immunocytochemical method in 10% to 15% of the cells at day 3 and day 5 after infection. Infectivity of in vitro-propagated HBV was demonstrated by infection of the naive FTO 9.1 cells with the culture supernatant from HBV-carrier cultures. In contrast to primary cultures of human hepatocytes and FTO 9.1 cells, primary rat and mouse hepatocytes, as well as rat hepatoma cell lines that do not express hA-V, are not susceptible to HBV infection. These findings suggest that hA-V plays a key role in the initial step of HBV infection and that the species-specific susceptibility to HBV infection and replication in hepatocytes is associated with the expression of hA-V.
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PMID:Transfection of a rat hepatoma cell line with a construct expressing human liver annexin V confers susceptibility to hepatitis B virus infection. 991 38

Previously, we have shown that small hepatitis B surface antigen (SHBsAg) binds specifically to human annexin V (hAV) and that hAV plays a key role in the initial steps of hepatitis B virus (HBV) infection. We have also demonstrated the spontaneous development of anti-idiotypic antibodies (antibodies to HBsAg Ab2) in rabbits immunized with hAV. As Ab2 is able to inhibit the binding of hAV to SHBsAg, Ab2 might contain epitope(s) mimicking a region of hAV for binding to SHBsAg. Identification of this epitope will therefore reveal a SHBsAg sequence involved in hAV binding. Using a panel of synthetic peptides covering the region of SHBsAg located on the outer surface of the virus, binding studies showed that the region incorporating amino acids (aa) 125-131 of SHBsAg is important for binding to Ab2 and consequently also for binding to hAV. Further experiments revealed that not only this region, but also the region incorporating aa 158-169, is involved in the binding of SHBsAg to hAV. As these regions are located in the structural vicinity according to the topological model of HBsAg proposed by Chen et al., our findings suggest that these regions are parts of a conformational epitope of SHBsAg for binding to hAV. Because of the crucial role of hAV in HBV infection, further studies on the HBsAg epitopes for hAV binding may lead to the development of a new generation of vaccines or molecules for prevention and for treatment of patients with chronic hepatitis B.
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PMID:Characterization of small hepatitis B surface antigen epitopes involved in binding to human annexin V. 1060 42

Previously, we have determined that human annexin V (hAV), a Ca2+-dependent phospholipid-binding protein, and not rat AV, binds specifically to small hepatitis B surface antigen (SHBsAg), and that transfection of a rat hepatoma cell line with a construct containing the hAV gene led to hAV expression and conferred susceptibility to hepatitis B virus (HBV) infection. In this work, we have examined the effect of administration of hAV on in vitro binding of SHBsAg to human and to rat hepatocytes and on in vitro HBV infection. The results showed that hAV could bind to human as well as to rat hepatocytes. Because of this property, excess hAV was unable to prevent HBV infection in primary cultures of human hepatocytes. On the other hand, it enabled rat hepatocytes to specifically bind SHBsAg and conferred susceptibility to HBV infection. After infection of primary cultures of rat hepatocytes in the presence of hAV, HBV mRNA, covalently closed circular (ccc) DNA, replicative intermediates, hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and secreted HBV DNA were detected. After infection in the absence of hAV, no markers of HBV replication were detected. Hence, from the present study we conclude that hAV is involved in facilitating HBV entry, leading to successful HBV infection in primary cultures of rat hepatocytes, while it is not effective in preventing HBV infection in primary cultures of human hepatocytes.
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PMID:Influence of the administration of human annexin V on in vitro binding of small hepatitis B surface antigen to human and to rat hepatocytes and on in vitro hepatitis B virus infection. 1076 40

This review elaborates on the known interactions of annexins with some viral pathogens of man. The best documented interactions are those between human cytomegalovirus and annexin II, and hepatitis B virus and annexin V. The review starts with a description of some structural considerations and potential functions of these annexins before going into a more detailed analysis of the viral interactions themselves. Finally, some questions relating to the suitability of these interactions as a drug target are touched upon.
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PMID:Interaction of viruses with annexins: a potential therapeutic target? 1124 92


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