Hepatitis B virus (HBV) promoters are regulated by the HBV enhancer in a tissue-specific manner

Antonucci, Tammy K.; Rutter, William J.

doi:10.1128/jvi.63.2.579-583.1989

Cited by 110 publications

(46 citation statements)

References 31 publications

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“…As we know, various HBV products are regulated by different regulatory sequences, including four promoters, that is, the preS1 promoter, preS2 promoter, X promoter, and core promoter, as well as two enhancers (enhancer I and II). In addition, two enhancers could regulate the activity of four promoters [54]. Therefore, the current data demonstrated that doxorubicin promotes HBV replication by enhancing the activity of all four promoters.…”

Section: Discussionsupporting

confidence: 50%

RFX1 participates in doxorubicin‐induced hepatitis B virus reactivation

et al. 2018

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Cytotoxic chemotherapy drugs, including doxorubicin, can directly promote hepatitis B virus (HBV) replication, but the mechanism has not been fully clarified. This study investigated the potential mechanism underlying the cytotoxic chemotherapy‐mediated direct promotion of HBV replication. We found that HBV replication and regulatory factor X box 1 gene (RFX1) expression were simultaneously promoted by doxorubicin treatment. The amount of RFX1 bound to the HBV enhancer I was significantly increased under doxorubicin treatment. Furthermore, the activity of doxorubicin in promoting HBV replication was significantly attenuated when the expression of endogenous RFX1 was knocked down, and the EP element of HBV enhancer I, an element that mediated the binding of RFX1 and HBV enhancer I, was mutated. In addition, two different sequences of the conserved EP element were found among HBV genotypes A‐D, and doxorubicin could promote the replication of HBV harboring either of the conserved EP elements. Here, a novel pathway in which doxorubicin promoted HBV replication via RFX1 was identified, and it might participate in doxorubicin‐induced HBV reactivation. These findings would be helpful in preventing HBV reactivation during anticancer chemotherapy.

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Section: Discussionsupporting

confidence: 50%

RFX1 participates in doxorubicin‐induced hepatitis B virus reactivation

et al. 2018

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“…Previous report elucidated the existence of pregenomic/preC RNA or preS mRNA in HCC but did not identify an HBx mRNA transcript [20,21]. The promoter analysis of HBV DNA reveals that the innate promoter activity of HBx gene is actually high but the production of HBx mRNA in HBV-replicating cells is drastically repressed [31,32]. Therefore, it seems that the expression of HBx gene in human liver tissues is generally repressed but may be altered in some hepatocytes under different cellular microenvironments.…”

Section: Discussionmentioning

confidence: 93%

Expression of hepatitis B virus X protein is closely correlated with the high periportal inflammatory activity of liver diseases

Jin

Yun

Park

et al. 2001

Journal of Viral Hepatitis

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Hepatitis B virus X (HBx) protein is a multifunctional protein that exerts dual activity on cell proliferation and death. Although HBx is thought to be a major determinant that leads to hepatocellular carcinoma, its pathophysiological role in humans remains to be established. Attempts have been made to evaluate the role of HBx in liver specimens derived from patients with chronic B viral hepatitis and hepatocellular carcinoma. Among 25 paired liver specimens of hepatocellular carcinoma and corresponding nontumour liver tissues, HBx mRNA was hardly detected and was significantly lower than other HBV transcripts. An immunohistochemical study demonstrated that expression of HBx protein was also lower than other HBV gene products. Interestingly, however, expression of HBx protein changed with the progression of chronic hepatitis. HBx was expressed in 5.0% of patients with chronic hepatitis without cirrhosis but increased to 44.8% in chronic hepatitis with cirrhosis. In contrast, only one (3.7%) of 27 hepatocellular carcinomas showed HBx positivity whereas 29.6% of surrounding nontumour tissues was still HBx‐positive. These results suggest that HBx may play a major role at the promotion stage of carcinogenesis. Noticeably, HBx‐positive cells were preferentially localized in the periportal region of chronic hepatitis or periphery of cirrhotic nodules where high necroinflammatory activity was accompanied. We found a positive correlation between HBx expression and periportal inflammatory activity (P < 0.001). Thus, HBx may potentiate cell destruction and regeneration of liver that provide an opportunity for the accumulation of genetic mutations, which contribute to multistep hepatocarcinogenesis.

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“…Conflicting results regarding the effect of HBxAg on transcription from the subgenomic promoters in the context of the complete transcription unit have been reported by Zhou and Yen [1990], and in two other reports the data were not shown in support of statements that the subgenomic mRNA promoters are not targets for transactivation by HBxAg Twu et al, 1989aI. Transcription under control of either subgenomic promoter is activated by enhancer(1) [Bulla and Siddiqui, 1988;De-Medina et al, 1988;Faktor et al, 1988;Antonucci and Rutter, 1989;1989;Hu and Sid-Hepatitis B Virus X-Gene Product diqui, 1991 ] which, as described above, serves as a target for transactivation by HBxAg when associated with a homologous or heterologous promoter fused to a reporter gene.…”

Section: Neweelgeeirlkvpvlcgcrhklvcspapcnfftsa Tkweegsidprzsipcrhk--mentioning

confidence: 98%

Hepatitis B virus X‐gene product: A promiscuous transcriptional activator

Rossner

1992

Journal of Medical Virology

203

133

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The disease state induced by infection with hepatitis B virus (HBV) is manifest in varying ways characterised by the extent of liver inflammation and damage and viral persistence. In a small percentage of cases, primary infection leads to fulminant hepatitis resulting in severe liver dysfunction with very high mortality. Primary infection is most often resolved by complete clearance of the virus and development of immune memory to counter reinfection, but 5‐10% of infected adults develop chronic infection characterised by the persistence of viral antigens in the serum and accompanied by varying degrees of hepatic injury. This disease state may continue after integration of HBV DNA into the hepatocyte genome from which transcription of viral antigen genes may continue in the absence of virion production. Chronically infected patients are predisposed to developing hepatocellular carcinoma (HCC) [Szmuness, 1978] with more than 100‐fold greater probability than non‐infected individuals [Beasley, et al., 1981]. Hepatitis B constitutes a major worldwide health problem with the number of chronically infected people currently estimated in excess of 250 million. HBV is the prototype member of the family of hepadnaviridae, which includes hepatitis viruses isolated from the woodchuck (WHV) [Summers et al., 1978], ground squirrel (GSHV) [Marion et al., 1980], Pekin duck (DHBV) [Mason et al., 1980], and grey heron (HHV) [Sprengel et al., 1988]. This taxonomy is derived from the relative hepatropism of virus family members, their common virion morphology, genome size, structure and organisation, and common mechanism of genome replication, which proceeds through reverse transcription of an RNA intermediate [Summers and Mason, 1982] in a manner analogous to that of retroviruses. All the viruses exhibit a strict host specificity, the human virus replicating only in man and a small number of higher apes. HBV has a partially double stranded, open‐circular genome of 3.2 kilobases (kb) which contains four open reading frames (ORFs) including the S‐gene encoding the surface antigen and the C‐gene encoding the core antigen (Fig. 1 ). A large ORF encompassing most of the viral genome encodes the viral polymerase while the fourth ORF encodes a protein of 154 amino acid residues which has been termed the X antigen (HBxAg) because the function of this product in the viral lifecycle is still under intensive investigation.

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Hepatitis B virus (HBV) promoters are regulated by the HBV enhancer in a tissue-specific manner

Cited by 110 publications

References 31 publications

RFX1 participates in doxorubicin‐induced hepatitis B virus reactivation

RFX1 participates in doxorubicin‐induced hepatitis B virus reactivation

Expression of hepatitis B virus X protein is closely correlated with the high periportal inflammatory activity of liver diseases

Hepatitis B virus X‐gene product: A promiscuous transcriptional activator

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