The expression of hepatitis B spliced protein (HBSP) encoded by a spliced hepatitis B virus RNA is associated with viral replication and liver fibrosis

Soussan, Patrick Ben; Tuveri, Rosella; Nalpas, Bertrand; Garreau, Florianne; Zavala, Flora; Masson, Annie; Pol, Stanislas; Bréchot, Christian; Kremsdorf, Dina

doi:10.1016/s0168-8278(02)00422-1

Cited by 101 publications

(97 citation statements)

References 23 publications

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“…In vitro, HBSP expression induces apoptosis without cell-cycle block (Soussan et al, 2000). More recently, HBSP protein expression was correlated with viral replication and with the onset of hepatic fibrosis (Soussan et al, 2003). Furthermore, the correlation between the detection of anti-HBSP antibodies and fibrosis was independent of viral replication.…”

Section: Hbv-related Hcc D Kremsdorf Et Almentioning

confidence: 99%

“…In vivo, HBSP protein has been detected in liver biopsy specimens from patients with active chronic hepatitis. In addition, antibodies directed against this protein have been found in the serum of approximately 45% of patients with chronic hepatitis (Soussan et al, 2000(Soussan et al, , 2003. In vitro, HBSP expression induces apoptosis without cell-cycle block (Soussan et al, 2000).…”

Section: Hbv-related Hcc D Kremsdorf Et Almentioning

confidence: 99%

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Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

et al. 2006

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As discussed in detail in other chapters of this review, chronic hepatitis B (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other, being much higher in the southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated with the cirrhosis. This heterogeneity is probably a reflection of different environmental and genetic factors. This review will summarize the current knowledge on the mechanisms involved in HBVrelated liver carcinogenesis. It will show in particular how viruses can be viewed as tools to discover and dissect new cellular pathways involved in cancer development and emphasize the potential synergistic effects between HBV and hepatitis C virus, as well as between viral infections and other environmental factors, such as alcohol.

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Section: Hbv-related Hcc D Kremsdorf Et Almentioning

confidence: 99%

Section: Hbv-related Hcc D Kremsdorf Et Almentioning

confidence: 99%

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

et al. 2006

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“…L* has also been shown to have antiapoptotic activity in infected macrophages (112,113). A new HBV protein, known as HBSP (HBV spliced-generated protein), has recently been discovered and implicated in advanced liver disease and viral persistence, possibly through its effect on cell apoptosis signaling and/or anti-viral activity (114,115).…”

Section: Possible Functional Relationships With Other Viral Proteinsmentioning

confidence: 99%

The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product

Vassilaki

Mavromara

2009

IUBMB Life

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Hepatitis C virus (HCV) is an enveloped positive‐strand RNA virus of the Flaviviridae family. It has a genome of about 9,600 nucleotides encoding a large polyprotein (about 3,000 amino acids) that is processed by cellular and viral proteases into at least 10 structural and nonstructural viral proteins. A novel HCV protein has also been identified by our laboratory and others. This protein—known as ARFP (alternative reading frame protein), F (for frameshift) or core+1 (to indicate the position) protein ‐ is synthesized by an open reading frame overlapping the core gene at nucleotide +1 (core+1 ORF). However, almost 10 years after its discovery, we still know little of the biological role of the ARFP/F/core+1 protein. Abolishing core+1 protein production has no affect on HCV replication in cell culture or uPA‐SCID mice, suggesting that core+1 protein is probably not important for the HCV reproductive cycle. However, the detection of specific anti‐core+1 antibodies and T‐cell responses in HCV‐infected patients, as reported by many independent laboratories, provides strong evidence that this protein is produced in vivo. Furthermore, analyses of the HCV sequences isolated from patients with hepatocellular carcinoma and in vitro studies have provided strong preliminary evidence to suggest that core+1 protein plays a role in advanced liver disease and liver cancer. The available in vitro data also suggest that certain core function proteins may depend on production of the core+1 protein. We describe here the discovery of the various forms of the core+1 protein and what is currently known about the mechanisms of their production and their biochemical and functional properties. We also provide a detailed summary of the results of patient‐based research. © 2009 IUBMB IUBMB Life, 61(7): 739–752, 2009

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“…It is possible that dHBV particles may serve as a decoy to mop up neutralizing antibodies produced against HBV, thereby allowing immune escape of the WT virus. Our finding of higher pgRNA levels in dHBV genomes may be explained, at least in part, by clinical studies linking HBSP to higher HBV DNA levels (Soussan et al, 2003).…”

Section: Resultsmentioning

confidence: 74%

“…Higher dHBV : HBV ratios in patients with chronic HBV infection have been associated with severe liver necrosis and fibrosis (Soussan et al, 2008). In addition, the expression of HBSP has been linked to higher HBV DNA levels (Preiss et al, 2008;Soussan et al, 2003). Recent clinical studies linking dHBV to virus loads and liver disease have renewed the interest in dHBV.…”

Section: Introductionmentioning

confidence: 99%

Enhanced hepatitis B virus (HBV) pre-genomic RNA levels and higher transcription efficiency of defective HBV genomes

Kandpal

Samal

Biswas

et al. 2015

Journal of General Virology

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Defective hepatitis B virus (dHBV) particles contain genomes corresponding to singly spliced HBV RNA. A limited number of studies show that dHBV is present in all chronically HBVinfected patients. Clinical studies have linked dHBV and dHBV gene products to high virus loads and liver damage. The replication characteristics of dHBV genomes remain poorly understood. We found that the splice donor/acceptor sites critical for the formation of dHBV genomes are conserved across HBV genotypes. We report a novel method to create dHBV constructs from corresponding wild-type (WT) HBV constructs. We assessed the transcriptional characteristics of the dHBV constructs with those of the corresponding WT construct using a cell culture model. Interestingly, dHBV constructs had higher pre-genomic RNA levels, transcription efficiency, HBV e antigen levels and intracellular HBV core antigen levels compared with the corresponding WT HBV constructs. Our findings highlight previously unrecognized fundamental molecular characteristics of dHBV genomes and their potential role in the pathogenesis of HBV infection.

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The expression of hepatitis B spliced protein (HBSP) encoded by a spliced hepatitis B virus RNA is associated with viral replication and liver fibrosis

Cited by 101 publications

References 23 publications

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis

The HCV ARFP/F/core+1 protein: Production and functional analysis of an unconventional viral product

Enhanced hepatitis B virus (HBV) pre-genomic RNA levels and higher transcription efficiency of defective HBV genomes

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