scholarly journals T1764G1766 core promoter double mutants are restricted to Hepatitis B virus strains with an A1757 and are common in genotype D

2005 ◽  
Vol 86 (9) ◽  
pp. 2451-2458 ◽  
Author(s):  
Hossein Sendi ◽  
Marjan Mehrab-Mohseni ◽  
Mohammad R. Zali ◽  
Helene Norder ◽  
Lars O. Magnius
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Binding Site ◽  
Core Promoter ◽  
Basal Core Promoter ◽  
Double Mutation ◽  
Virus Load ◽  
B Virus ◽  
Nuclear Factor 1 ◽  
Promoter Mutations

To investigate the role of pre-core and basal core promoter (BCP) mutants in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB) in Iran, Hepatitis B virus strains from 30 patients and 42 anti-HBe-positive asymptomatic carriers (ASCs) were characterized. G1896A pre-core stop mutants, detected in 77 % of e-CHB patients and 85 % of ASCs, showed no association with virus load or aminotransferase levels. Twenty per cent of e-CHB patients and 31 % of ASCs harboured T1762A1764 mutants. When this double mutation was associated with G1757, it was linked to a higher virus load in patients than when it was associated with A1757 (105·2±1·8 vs 103·2±0·8 copies ml−1; P=0·004). Interestingly, the most common BCP mutations were T1764 and G1766, which were present in 33 % of e-CHB patients and 29 % of ASCs. These were associated with higher virus load and aminotransferase levels compared with patients lacking core promoter mutations, although this was not significant. The T1764G1766 double mutation was only present in strains with A1757 (P<0·001), which is more frequent in strains of genotype D than in those belonging to other genotypes. On the other hand, the T1762A1764 double mutation was found more frequently in association with G1757 than with A1757. The T1762A1764 double mutation forms a binding site for hepatocyte nuclear factor 1 (HNF1), which is constrained by A1757. However, the T1764G1766 double mutant may form a binding site for HNF3. Thus, position 1757 affects the emergence of promoter double mutants and would predict a relative genotypic restriction of both the T1762A1764 and the T1764G1766 double mutants.

scholarly journals Regulation of Hepatitis B Virus Core Promoter by Transcription Factors HNF1 and HNF4 and the Viral X Protein

2004 ◽  
Vol 78 (13) ◽  
pp. 6908-6914 ◽  
Author(s):  
Yanyan Zheng ◽  
Jie Li ◽  
Jing-hsiung Ou
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Binding Site ◽  
Nuclear Receptors ◽  
Double Mutant ◽  
Core Promoter ◽  
X Protein ◽  
Double Mutation ◽  
The Core ◽  
B Virus

ABSTRACT Hepatitis B virus (HBV) core promoter contains a binding site for nuclear receptors. A natural double mutation in this binding site, which changes nucleotide (nt) 1765 from A to T and nt 1767 from G to A, selectively abolishes the binding of several nuclear receptors without affecting that of HNF4. This double mutation also creates a binding site for the transcription factor HNF1 and changes two amino acids in the overlapping X protein sequence. In this study, we have examined the roles of HNF1, HNF4, and the X protein in the regulation of the core promoter activities in Huh7 hepatoma cells. Our results indicate that HNF4 could stimulate the expression of the precore RNA and the core RNA from the core promoter of both the wild-type (WT) HBV and the double mutant, although its effect on the former was more prominent. In contrast, HNF1, which did not affect the WT core promoter, suppressed the precore RNA expression of the double mutant. Further analysis using HBV genomic constructs, with and without the ability to express the X protein, indicates that the X protein did not affect the HNF4 activity on the core promoter and affected the HNF1 activity on the core promoter of only the double mutant. Thus, our results indicate that the phenotypic differences of HBV WT and double-mutant core promoters are at least partially due to the differential activities of HNF1, HNF4, and the X protein on these two promoters.

Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers

2003 ◽  
Vol 124 (2) ◽  
pp. 327-334 ◽  
Author(s):  
Jia–Horng Kao ◽  
Pei–Jer Chen ◽  
Ming–Yang Lai ◽  
Ding–Shinn Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Promoter ◽  
Basal Core Promoter ◽  
B Virus ◽  
Promoter Mutations

Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia

2009 ◽  
Vol 15 (32) ◽  
pp. 3428
Author(s):  
Andi Utama ◽  
Sigit Purwantomo ◽  
Marlinang Diarta Siburian ◽  
Rama Dhenni ◽  
Rino Alvani Gani ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Promoter ◽  
Basal Core Promoter ◽  
B Virus ◽  
Promoter Mutations

Effects of hepatitis B virus precore and basal core promoter mutations on the expression of viral antigens: genotype B vs C

2011 ◽  
Vol 18 (10) ◽  
pp. e482-e490 ◽  
Author(s):  
C.-J. Liu ◽  
H.-R. Cheng ◽  
C.-L. Chen ◽  
T.-C. Chen ◽  
T.-C. Tseng ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Promoter ◽  
Basal Core Promoter ◽  
Viral Antigens ◽  
B Virus ◽  
Promoter Mutations

scholarly journals Effects of Hepatitis B Virus Mutations on its Replication and Liver Disease Severity

2013 ◽  
Vol 7 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Abdulrahim Hakami ◽  
Abdelwahid Ali ◽  
Ahmed Hakami
Keyword(s):  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Disease Severity ◽  
Chronic Infection ◽  
Core Promoter ◽  
Basal Core Promoter ◽  
Double Mutation ◽  
B Virus ◽  
Genotype C

Hepatitis B virus (HBV), nowadays, is one of the major human pathogens worldwide. Approximately, 400 million people worldwide have chronic HBV infection. Only 5% of persons infected during adulthood develop chronic infection. The reverse is true for those infected at birth or in early childhood, i.e. more than 90% of these persons progress to chronic infection. Currently, eight different genotypes o f HBV have been identified, differing in nucleotide sequence by greater than 8%. In addition, numerous subgenotypes have a l s o been recognized based on the nucleotide sequence variability of 4- 8%. It has invariably been found that these genotypes and mutations play a pivotal role in the liver disease aggravation and virus replication. The precore mutations (G1896A) and the double mutation (T1762/A1764) in the basal core promoter are important mutations that alter expression of the hepatitis B e antigen (HBeAg). The HBeAg is important for establishing viral persistence. The precore G1896A mutation abrogates the expression of HBeAg. Numerous other mutations alter the disease severity and progression. It is predictive that the infected patient has high risk of hepatocellular carcinoma if the genotype C is incriminated or if HBV possesses basal core promoter double mutation. Association of the remaining genotypes have been noted but with less degree than genotype C. Phenotypic assays of the different HBV protein markers with different molecular techniques illustrate the replication efficiency of the virus in cell lines. This review will discuss various mutations into their association with liver disease severity and progression as well as virus replication.

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