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

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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Association of hepatitis B virus subgenotypes and basal core promoter/precore region variants with the clinical features of patients with acute hepatitis

Journal of Gastroenterology ◽

10.1007/s00535-008-2197-2 ◽

2008 ◽

Vol 43 (7) ◽

pp. 558-564 ◽

Cited By ~ 25

Author(s):

Kazuhiko Hayashi ◽

Yoshiaki Katano ◽

Yasushi Takeda ◽

Takashi Honda ◽

Masatoshi Ishigami ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Acute Hepatitis ◽

Clinical Features ◽

Core Promoter ◽

Basal Core Promoter ◽

Precore Region ◽

B Virus

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

The Open Virology Journal ◽

10.2174/1874357901307010012 ◽

2013 ◽

Vol 7 (1) ◽

pp. 12-18 ◽

Cited By ~ 11

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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Molecular characterization of Hepatitis B virus basal core promoter and precore region of isolates from chronic Hepatitis B patients

Journal of the Pakistan Medical Association ◽

10.47391/jpma.1254 ◽

2021 ◽

pp. 1-18

Author(s):

Israr Ahmad ◽

Kafeel Ahmad

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Phylogenetic Tree ◽

Chronic Hepatitis B ◽

Stop Codon ◽

Core Promoter ◽

Direct Sequencing ◽

Basal Core Promoter ◽

Double Mutation ◽

Precore Region

Abstract Objective: The aim of this study was to analyze mutations in precore/core promoter region of HBV genome in chronic hepatitis B patients from three cities of Pakistan. Methods: A total of 50 treatment naïve chronic hepatitis B patients from Pakistan were selected. Viral load, HBeAg/antiHBe status, HBV ELISA and ALT levels were determined. Direct sequencing of BCP and PC region of HBV genome was carried out following a nested PCR approach. Phylogenetic tree was constructed using MEGA software version 6.0. Statistical analysis was carried out using SPSS version 16.0. Results: The G1896A precore stop codon mutation was detected in 19 (38%) isolates. The mutation was present in 17(34%) isolates from HBeAg negative patients and 2(4%) isolates from HBeAg positive patients. The Classic A1762T/G1764A double mutation was noted in 15 (30%) isolates. Mutation at position 1764 was observed in 12 (48%) samples. A rare G1764T mutation was also detected in 6 (12%) isolates. The CG1802-1803 mutation was detected in 47(94%) isolates. The T1858 mutation was detected in all 50 (100%) isolates. The GCAC Kozak sequence was present in 43(86%) isolates. The CAA1817-1819 mutation was observed in 49(98%) isolates and G1888 mutation was detected in 49(98%) isolates. Overall, 9(18%) isolates had wild-type sequences at all important loci including positions 1762,1764 and 1896. The pattern of sequences at genotype specific positions and phylogenetic tree revealed that majority of study isolates belonged to genotype D. Conclusions: Sequences results showed that precore region was comparatively more conserved than BCP region. Continuous...

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Association between hepatitis B virus basal core promoter/precore region mutations and the risk of hepatitis B-related acute-on-chronic liver failure in the Chinese population: an updated meta-analysis

Hepatology International ◽

10.1007/s12072-016-9716-7 ◽

2016 ◽

Vol 10 (4) ◽

pp. 606-615 ◽

Cited By ~ 12

Author(s):

Xueyuan Nian ◽

Zhihui Xu ◽

Yan Liu ◽

Jianhong Chen ◽

Xiaodong Li ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Liver Failure ◽

Chinese Population ◽

Core Promoter ◽

Meta Analysis ◽

Basal Core Promoter ◽

Chronic Liver Failure ◽

Precore Region ◽

B Virus

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Prevalence of Mutations in Basal Core Promoter and Precore Region of Hepatitis B Virus in Vaccinated and Nonvaccinated Individuals of the Aboriginal Nicobarese Tribe of Car Nicobar Island, India

Intervirology ◽

10.1159/000365756 ◽

2014 ◽

Vol 57 (6) ◽

pp. 357-364 ◽

Cited By ~ 2

Author(s):

Haimanti Bhattacharya ◽

Debdutta Bhattacharya ◽

Muruganandam Nagarajan ◽

Rajesh Reesu ◽

Subarna Roy ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Core Promoter ◽

Basal Core Promoter ◽

Nicobar Island ◽

Precore Region ◽

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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Effect of basal core promoter and pre-core mutations on hepatitis B virus replication

Journal of General Virology ◽

10.1099/vir.0.83468-0 ◽

2008 ◽

Vol 89 (4) ◽

pp. 901-909 ◽

Cited By ~ 81

Author(s):

Saffie Jammeh ◽

Fiona Tavner ◽

Roger Watson ◽

Howard C. Thomas ◽

Peter Karayiannis

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Virus Replication ◽

Stop Codon ◽

Core Promoter ◽

Replication Capacity ◽

Basal Core Promoter ◽

Appreciable Effect ◽

Huh7 Cells ◽

B Virus

There are two hypotheses explaining a fulminant outcome after hepatitis B virus (HBV) infection, both of which may be applicable at the same time: (i) basal core promoter (BCP) mutations increase viral replication, allowing rapid spread of the virus through the liver, and (ii) pre-core (pre-C) mutations abrogating hepatitis B e antigen (HBeAg) synthesis remove its tolerogenic effect, leading to a vigorous immune response. This study investigated the effect of these mutations on virus replication efficiency and HBeAg production. Substitutions A1762T/G1764A and T1753C, C1766T and T1768A in the BCP region, and G1896A and G1899A in the pre-C region, were examined either alone or in combination, using a common genetic background. Huh7 cells were transfected with these constructs and real-time PCR was used to quantify released virion-associated and intracellular HBV DNA, pregenomic RNA and pre-C mRNA. In addition, culture supernatants were tested for hepatitis B surface antigen (HBsAg) and HBeAg. The double BCP mutation (A1762T/G1764A) and the pre-C mutations (G1896A, G1899A), either alone or in combination, had no appreciable effect on the replication capacity of the virus. In contrast, clones with mutations at positions 1766/1768, 1762/1764/1766 and 1753/1762/1764 exhibited increased-replication phenotypes. HBeAg was undetectable in all cultures transfected with constructs bearing the G1896A stop-codon mutation, as expected. In contrast, constructs with additional mutations in the BCP region had appreciably lower levels of HBeAg expression than the wild type. Thus, core promoter mutations other than those at 1762/1764 appear to upregulate viral DNA replication and, at the same time, greatly reduce HBeAg production.

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