Frequency and distribution of hepatitis B virus genotypes among eastern Indian voluntary blood donors: Association with precore and basal core promoter mutations

Biswas, Avik; Chandra, Partha K.; Datta, Sibnarayan; Panigrahi, Rajesh; Banerjee, Arup; Chakrabarti, Shibdas; Biswas, Kalidas; P, Patra D; Bhattacharya, Partha Pratim; Biswas, Kuntal; Chakravarty, Runu

doi:10.1111/j.1872-034x.2008.00403.x

Cited by 21 publications

(25 citation statements)

References 34 publications

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“…In this study, we found that all detected strains showed mutations at nt 1726, nt 1730, nt 1802/1803, and nt 1850; the most frequent common mutation in BCP and PC regions was T1773 (97.5%), followed by C1773 (62.5%), A1896 (52.5%), T1703 (42.5%), C1753 (32.5%), A1899 (30%) and T1762/A1764 (27.5%). Among host-virus interactions which were involved in the pathogenesis of the HBV, the relevance of naturally occurring viral variants in PC/C regions was reported in some studies (25-27) and their presence was associated with the wide spectrum of clinical patterns ranging from an asymptomatic chronic state to self-limited acute hepatitis, or fulminant to chronic hepatitis with progression to liver cirrhosis and hepatocellular carcinoma (28-31). At present, it is well established that the host immune response is the key determinant influencing the course of disease and the onset of liver disease (25).…”

Section: Discussionmentioning

confidence: 99%

Investigation of DNA Sequence in the Basal Core Promoter, Precore, and Core Regions of Hepatitis B Virus from Tunisia Shows a Shift in Genotype Prevalence

Ayari¹,

Lakhoua-Gorgi²,

Bouslama

et al. 2012

Hepat Mon

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BackgroundIn this study, we evaluated the prevalence of the most common mutations occurring in Enhancer II (EnhII), Basal Core Promoter (BCP), Precore (PC), and Core (C) regions of hepatitis B virus (HBV) genome.ObjectivesWe also investigated the correlation between HBV variants, their genotypes, and patients’ HBe antigen (HBeAg: soluble shape of the capsid antigen) status.Patients and MethodsWe retrieved viral DNA from 40 serum samples of Tunisian patients positive for hepatitis B surface antigen (HBsAg) and HBV DNA, amplified the above mentioned regions using specific primers, and sequenced the corresponding PCR (polymerase chain reaction) products. For further analysis purpose, the patients were divided into two groups: Group1 including 34 HBeAg-negative patients and Group2 with 6 HBeAg-positive patients.ResultsTwenty-one patients (52.5%) showed PC G1896A mutation and 11 (27.5%) carried A1762T/G1764A double mutations. These mutations were more frequent in HBeAg-negative patients than that in HBeAg-positive ones. Indeed, 58.8% of patients bearing G1896A mutation were HBeAg-negative while 16.7% were positive. In patients bearing T1762/A1764 double mutation, 29.4% were positive and 16.7% were negative. In addition, the A1896 mutation was restricted to HBV isolates that had wild-type T1858, while C1858 was rather linked to the occurrence of T1762/A1764 mutation. Interestingly, this study revealed a high frequency of genotype E. This frequency was important as compared to that of genotype D known to be predominant in the country as delineated in previous studies.ConclusionsPrevious results supported and showed that HBV strains present in Tunisia belonging to genotype D and, to a lesser extent, to genotype E, were prone to mutations in BCP/ PC regions. This observation was more obvious in HBV isolates from asymptomatic chronic carriers (AsC). The high mutational rates observed in our study might result from a mechanism of viral escape that plays an important role in the loss of HBeAg.

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Section: Discussionmentioning

confidence: 99%

Investigation of DNA Sequence in the Basal Core Promoter, Precore, and Core Regions of Hepatitis B Virus from Tunisia Shows a Shift in Genotype Prevalence

Ayari¹,

Lakhoua-Gorgi²,

Bouslama

et al. 2012

Hepat Mon

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“…The HBV genotyping was initially done by a highly sensitive polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, as previously described [16]. The complete basal core promoter/precore (BCP/PC) (nt 1742–1900 from EcoR I site) region was amplified by nested PCR with first round primers ep1-1 (sense)/ep1-2 (antisense) and second round primers ep2-1 (sense)/ep2-2 (antisense) whereas the complete core gene (nt 1901–2452 from EcoR I site) was amplified using the primers HB7F (sense)/HBAS6 (antisense) for the first round and CB3 (sense)/HBAS5 (antisense) for the second round.…”

Section: Methodsmentioning

confidence: 99%

“…The first fragment includes the whole PreS1/S2 region which was amplified as described earlier [17] while the second fragment, spanning the entire S gene, was amplified using primers HB1F (sense)/HS4R (antisense) for the first round and B2 (sense)/HS4R (antisense) for the second round. The above reactions were performed using Promega Taq DNA polymerase (Promega, Madison, WI) and all the reagent concentrations were maintained as per the earlier methods [16]. Details of all the primers and their respective thermal profiles are presented in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India

et al. 2014

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Previously we reported that the exposure to hepatitis B virus (HBV) infection serves as a major threat among the treatment naive HIV infected population of eastern India. Hence, molecular characterization of these strains is of utmost importance in order to identify clinically significant HBV mutations. A total of 85 treatment naive HIV/HBV co-infected participants were included of whom the complete basal core promoter/precore region, the core and the whole envelope gene could be successfully sequenced for 59, 57 and 39 isolates respectively. Following phylogenetic analysis, it was found that HBV/D was the predominant genotype with HBV/D2 (38.5%) being the most prevalent subgenotype followed by HBV/A1. The major mutations affecting HBeAg expression includes the A1762T/G1764A (13.6%), G1896A (22%) and G1862T mutation (33.9%) which was predominantly associated with HBV/A1. Moreover, the prevalence of G1896A was considerably high among the HBeAg negative HIV/HBV co-infected subjects compared to HBV mono-infection. The main amino acid substitutions within the MHC class II restricted T-cell epitope of HBcAg includes the T12S (15.8%) and T67N (12.3%) mutation and the V27I (10.5%) mutation in the MHC class I restricted T-cell epitope. PreS1/S2 deletion was detected in 3 isolates with all harboring the BCP double mutation. Furthermore, the frequently occurring mutations in the major hydrophilic loop of the S gene include the T125M, A128V and M133I/L. Therefore, this study is the first from India to report useful information on the molecular heterogeneity of the HBV strains circulating among the treatment naive HIV/HBV co-infected population and is thus clinically relevant.

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“…HBV genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, as previously described [10]. The results of PCR-RFLP were further confirmed by means of direct sequencing with Prism Big Dye kit and ABI 3130×l Genetic Analyzer (Applied Biosystems, Foster City, USA).…”

Section: Methodsmentioning

confidence: 99%

Characterization of Treatment-Naive HIV/HBV Co-Infected Patients Attending ART Clinic of a Tertiary Healthcare Centre in Eastern India

et al. 2013

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ObjectiveThe study was designed to assess the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection scenario among the human immunodeficiency virus (HIV) infected patients attending a tertiary healthcare unit in eastern India. Additionally, clinical and virological characterization of these viruses, prior to antiretroviral therapy (ART) initiation was also done for better understanding of the disease profile.MethodsPool of ART-naive HIV/HBV co-infected and HIV mono-infected patients, participating in two different studies, were included in this study. HBV DNA was detected by nested-PCR amplification followed by HBV genotype determination and HBV reverse transcriptase (RT) region amplification and direct sequencing for detecting drug resistance.ResultsThe prevalence of HBsAg (11.3%) was higher compared to anti-HCV (1.9%) among the HIV infected ART-naive patients. Moreover, majority of the HBeAg positive HIV/HBV co-infected patients (87.7%) had HBV DNA ≥20,000 IU/ml with median HBV DNA significantly higher than that of HBeAg negative subjects (5.7 log10 IU/ml vs. 4.2 log10 IU/ml; p<0.0001). Multivariate analysis also showed that HBeAg-positive status was independently associated with higher HBV DNA level (p = <0.001). Notably, 60.9% of the HBeAg negative co-infected subjects had HBV DNA ≥2,000 IU/ml of which 37.0% had HBV DNA ≥20,000 IU/ml. Genotype HBV/D (68.2%) was the predominant genotype followed by HBV/A (24.3%) and HBV/C (7.5%). Anti-HBV drug resistant mutations were detected in two (3.8%) of the ART-naive patients.ConclusionThe prevalence of HIV/HBV co-infection was relatively higher in our study subjects. HBeAg testing might provide clue for early treatment initiation. Furthermore, HBeAg negative patients are also associated with high HBV DNA levels and therefore require appropriate medical attention. Pre-treatment screening for anti-HBV drug resistant mutations is not necessary before ART initiation.

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Frequency and distribution of hepatitis B virus genotypes among eastern Indian voluntary blood donors: Association with precore and basal core promoter mutations

Abstract: In addition to HBV/D and HBV/A, a significant proportion of HBV/C (23.4%) was also present among the voluntary blood donors from eastern India, most frequently in the 18-25 year age group. BCP mutation was more common in HBV/C infected donors.

Cited by 21 publications

References 34 publications

Investigation of DNA Sequence in the Basal Core Promoter, Precore, and Core Regions of Hepatitis B Virus from Tunisia Shows a Shift in Genotype Prevalence

Investigation of DNA Sequence in the Basal Core Promoter, Precore, and Core Regions of Hepatitis B Virus from Tunisia Shows a Shift in Genotype Prevalence

Molecular Characterization of HBV Strains Circulating among the Treatment-Naive HIV/HBV Co-Infected Patients of Eastern India

Characterization of Treatment-Naive HIV/HBV Co-Infected Patients Attending ART Clinic of a Tertiary Healthcare Centre in Eastern India

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