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

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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Association of hepatitis B virus mutations in basal core promoter and precore regions with severity of liver disease: an investigation of 793 Chinese patients with mild and severe chronic hepatitis B and acute-on-chronic liver failure

Journal of Gastroenterology ◽

10.1007/s00535-010-0315-4 ◽

2010 ◽

Vol 46 (3) ◽

pp. 391-400 ◽

Cited By ~ 51

Author(s):

Zhihui Xu ◽

Xiaoqiang Ren ◽

Yan Liu ◽

Xiaodong Li ◽

Siyu Bai ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Disease ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Core Promoter ◽

Chinese Patients ◽

Basal Core Promoter ◽

Chronic Liver Failure ◽

B Virus ◽

Severe Chronic Hepatitis

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Specific mutations of basal core promoter are associated with chronic liver disease in hepatitis B virus subgenotype D1 prevalent in Turkey

Microbiology and Immunology ◽

10.1111/1348-0421.12011 ◽

2013 ◽

Vol 57 (2) ◽

pp. 122-129 ◽

Cited By ~ 8

Author(s):

Mustafa Sunbul ◽

Masaya Sugiyama ◽

Fuat Kurbanov ◽

Hakan Leblebicioglu ◽

Anis Khan ◽

...

Keyword(s):

Liver Disease ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Liver Disease ◽

Core Promoter ◽

Chronic Liver ◽

Basal Core Promoter ◽

B Virus

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Sequential Accumulation of the Basal Core Promoter and the Precore Mutations in the Progression of Hepatitis B Virus-Related Chronic Liver Disease

Intervirology ◽

10.1159/000093456 ◽

2006 ◽

Vol 49 (5) ◽

pp. 266-273 ◽

Cited By ~ 26

Author(s):

Byung-Cheol Song ◽

Xiu Ji Cui ◽

Heung Up Kim ◽

Yoo-Kyung Cho

Keyword(s):

Liver Disease ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Chronic Liver Disease ◽

Core Promoter ◽

Chronic Liver ◽

Basal Core Promoter ◽

B Virus

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

Journal of General Virology ◽

10.1099/vir.0.81023-0 ◽

2005 ◽

Vol 86 (9) ◽

pp. 2451-2458 ◽

Cited By ~ 26

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.

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Prevalence of Hepatitis B Virus (HBV) Basal Core Promoter/Precore region molecular variants among HIV/HBV co-infected and HBV mono-infected patients in Ile-Ife, Nigeria

10.1101/2020.07.16.206151 ◽

2020 ◽

Author(s):

Oluwadamilola Gideon Osasona ◽

Lydia Boudarene ◽

Opeoluwa Adewale-Fasoro ◽

Uwem George ◽

Judith Oguzie ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Phenotypic Diversity ◽

Stop Codon ◽

Core Promoter ◽

Enzyme Linked Immunosorbent Assay ◽

Basal Core Promoter ◽

Double Mutation ◽

Precore Region ◽

B Virus

AbstractIntroductionEvolution of phenotypic diversity among viruses occurs as an escape mechanism against host immune pressure or drug selective pressure. Among HIV/HBV co-infected individuals, various HBV basal core promoter (BCP)/precore (PC) region molecular mutants had been reported with associated phenotypic defect in HBeAg production. The emergence of HBeAg negative variants of HBV in HIV co-infected individuals have profound implication on the diagnosis, management and prognosis of this subset of individuals. This includes delayed clearance of HBV, early development of adverse hepatic events such as liver cirrhosis and hepatocellular carcinoma. Currently, little is known about HBV BCP/PC region genomic heterogeneity in HIV/HBV co-infected patients in Nigeria. Therefore, this study was focussed on investigating evidence of precore/core region genomic variability among HIV/HBV co-infected patients in Nigeria.Materials and methodsA total of 40 patients (20 HIV/HBV co-infected and 20 HBV mono-infected samples) were enrolled into the study and subsequently tested for HBsAg, HBeAg and HBeAb using specific Enzyme-Linked Immunosorbent Assay (ELISA). The BCP/PC genome regions (nucleotides 1653-1959) were amplified using a nested PCR assay and then subjected to BCP/PC mutational analysis in genome sites affecting HBeAg expression especially at the BCP transcriptional and PC Translational stop codon sites.ResultsOverall, 5(83.3%) of the six exploitable sequences after analysis showed various BCP/PC mutations. Only 1(16.6%) sequence from an HIV/HBV co-infected patient had the BCP transcriptional (double mutation; A1762T/G1764A) mutant. Analysis of the PC translational stop codon showed 4 (66.6%) having the G1896A mutants while 33.3% (2) had G1899A mutants.ConclusionThis study has broadened the available evidence of BCP/PC region molecular mutants among HIV/HBV co-infected patients in Nigeria and assessed the difference of mutation prevalence in comparison with HBV mono-infected cohort. We therefore recommend that HIV/HBV co-infected patients be routinely screened for hepatitis B virus precore region mutants to improve their patient outcome.

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