Demonstration of pre-S polypeptides of hepatitis B virus in infected livers

Thung, Swan N.; Gerber, Michael A.; Kasambalides, Efthimios J.; Gilja, Bal K.; Keh, William; Gerlich, Wolfram H.

doi:10.1002/hep.1840060615

Cited by 29 publications

(20 citation statements)

References 17 publications

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“…27 Many previous studies have shown that the expression patterns of HBsAg correlate to the replicative stages of chronic HBV infection. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] At the early replicative stage or in patients with acute exacerbation of chronic HBV carriers, the expression of HBsAg manifests an inclusion-like pattern in classic GGH, which usually distribute singly in liver sections. [8][9][10] After the HBeAg seroconversion or at the nonreplicative stage, however, a novel expression pattern of marginal type HBsAg emerges and the HBsAg-expressing hepatocytes usually cluster in groups.…”

Section: Discussionmentioning

confidence: 99%

“…3A and B), representing the high replicative status of HBV infection, wild-type pre-S gene was identified in 4 (cases 1-4), pre-S1 deletion in 2 (cases 5 and 6), and the remaining 1 case (case 7), pre-S2 deletion. In 7 samples (cases 8-14) with intermediate replicative status, wild-type pre-S gene was recognized in 3 (cases 8, 9, and 11), pre-S1 deletion in 1 (case 10), pre-S2 deletion in 3 (cases [12][13][14]. Two cases had an additional clone harboring 2 separate deletion sites over the pre-S1 and pre-S2 regions.…”

Section: Identification Of Pre-s Deletion Mutants In Serum Samples Wimentioning

confidence: 99%

“…In the past years, many studies have documented the accumulation of pre-S1 or large surface antigen in the hepatocytes during chronic HBV infection. [12][13][14][15] The large (pre-S1), middle (pre-S2), and small (major) surface proteins have been found to be differentially expressed in hepatocytes at different stages of HBV replication. 13,14 Most liver samples from viremic carriers show a prevalence of 2 smaller surface proteins whereas the large surface antigen is the predominant intrahepatic protein in nonviremic carriers.…”

mentioning

confidence: 99%

“…[12][13][14][15] The large (pre-S1), middle (pre-S2), and small (major) surface proteins have been found to be differentially expressed in hepatocytes at different stages of HBV replication. 13,14 Most liver samples from viremic carriers show a prevalence of 2 smaller surface proteins whereas the large surface antigen is the predominant intrahepatic protein in nonviremic carriers. 14 Dienes et al 14 speculated that the accumulation of large surface protein is associated with the HBV integration event, which may increase the expression of pre-S1 by a highly active cellular promoter.…”

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confidence: 99%

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Prevalence and Significance of Hepatitis B Virus (Hbv) Pre–S Mutants in Serum and Liver At Different Replicative Stages of Chronic Hbv Infection

et al. 2001

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Several types of naturally occurring pre-S mutants in sera or liver tissues in patients with chronic hepatitis B virus (HBV) infection have been identified. To clarify the prevalence and significance of emergence of pre-S mutants, 140 sera and 18 resected livers from patients with HBV were studied. Replicative status was designated as high, intermediate, and low based on the HBV-DNA levels in serum or the expression of HBV antigens in liver. In vitro transfection and Western blot analysis were performed to characterize expression and secretion of HBsAg by the mutant constructs. Five major types (I to V) of pre-S deletion mutants in serum and liver and 2 types (VI and VII) in liver were identified. Pre-S mutant was 6.4% at high replicative phase, 13% at intermediate, and 37.5% at low or nonreplicative phases in serum. In livers, the same tendency existed: pre-S2 deletion mutants emerged and prevailed at a low replicative phase in hepato- Hepatitis B virus (HBV) is a small, enveloped DNA virus that causes acute and chronic liver diseases. The majority of acute HBV infection are usually self-limited, whereas patients with chronic HBV infection usually pursue a life-long course that can be categorized into 3 phases based on the replicative status of HBV in serum and liver. [1][2][3][4][5][6][7][8][9] In the early or high replicative phase, there are high levels of hepatitis B e antigen (HBeAg), hepatitis B surface antigen (HBsAg), and HBV DNA in serum and an active replication of HBV genome with nuclear expression of core antigen (HBcAg) in liver. 3,[8][9][10] The HBsAg-expressing hepatocytes or ground glass hepatocytes (GGH) are usually singly scattered in distribution. In the intermediate or immune clearance phase, there is an HLA-restricted cytotoxic T lymphocyte (CTL) response to viral antigen-expressing hepatocytes, which may result in a decrease of HBeAg and HBV DNA in serum. In the late or nonreplicative phase, there is a low titer or absence of viremia and an integration of HBV genomes in host cells. The serum HBsAg, albeit decreased in level, usually persists for life. Contrary to that at the active replicative stage, the HBsAg-containing hepatocytes are inversely increased and clustered in groups at the late or nonreplicative stage, usually associated with an absence of intrahepatic HBcAg expression. [9][10][11] The underlying mechanism of the life-long persistence of serum HBsAg and the novel discrepancy between the levels of HBsAg in serum and liver have not yet been clarified. In the past years, many studies have documented the accumulation of pre-S1 or large surface antigen in the hepatocytes during chronic HBV infection. [12][13][14][15] The large (pre-S1), middle (pre-S2), and small (major) surface proteins have been found to be differentially expressed in hepatocytes at different stages of HBV replication. 13,14 Most liver samples from viremic carriers show a prevalence of 2 smaller surface proteins whereas the large surface antigen is the predominant intrahepatic protein in nonviremic carriers. 14 ...

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Section: Discussionmentioning

confidence: 99%

Section: Identification Of Pre-s Deletion Mutants In Serum Samples Wimentioning

confidence: 99%

mentioning

confidence: 99%

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Prevalence and Significance of Hepatitis B Virus (Hbv) Pre–S Mutants in Serum and Liver At Different Replicative Stages of Chronic Hbv Infection

et al. 2001

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“…Immunohistochemical studies have demonstrated the presence of HBsAg (116,145,154,248,250,283,340), HBxAg (134,170,341,393,418), and, to a lesser extent, HBcAg (145,154,250,340) and pre-S (71,72,106,125,139,358,360) in tumor and/or nontumor liver cells of patients with PHC. These results imply that the expression of one or more HBV antigens may be significant in the pathogenesis of PHC.…”

Section: Hbv Gene Expression: Putative Roles In Phcmentioning

confidence: 99%

Hepatitis B virus infection and primary hepatocellular carcinoma

Feitelson

1992

Clin Microbiol Rev

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For many years, epidemiological studies have demonstrated a strong link between chronic hepatitis B virus (HBV) infection and the development of primary hepatocellular carcinoma (PHC). Other hepatocarcinogens such as hepatitis C virus and aflatoxin also contribute to hepatocarcinogenesis either in conjunction with HBV infection or alone. Cellular and molecular biological studies are providing explanations for the HBV-PHC relationship, and models are now being formulated to further test the relative importance of various factors such as viral DNA integration, activation of oncogenes, genetic instability, loss of tumor suppressor genes, and trans-activating properties of HBV to the pathogenesis of PHC. Further research will probably define more than a single mechanism whereby chronic HBV infection results in PHC.

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