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      An overview of molecular epidemiology of hepatitis B virus (HBV) in India

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      1 ,
      Virology Journal
      BioMed Central

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          Abstract

          Hepatitis B virus (HBV) is one of the major global public health problems. In India, HBsAg prevalence among general population ranges from 2% to 8%, placing India in intermediate HBV endemicity zone and the number of HBV carriers is estimated to be 50 million, forming the second largest global pool of chronic HBV infections. India is a vast country, comprised of multiracial communities with wide variations in ethnicity and cultural patterns, which is attributable to its geographical location, gene influx due to invasion and/or anthropological migrations in the past. Moreover, recent increase in trade, trafficking and use of illicit drugs has also considerably influenced the epidemiology of HBV, specifically in the eastern and north eastern parts of India. However, data on the molecular epidemiology of HBV in India is scanty. HBV genotypes A and D have been well documented from different parts of mainland India. Interestingly, in addition to genotypes A and D, genotype C having high nucleotide similarity with south East Asian subgenotype Cs/C1 strain, have been detected exclusively from eastern Indian HBV carriers, suggesting a recent introduction. Thus, compared to other parts of India, the molecular epidemiology of HBV is naturally distinct in eastern India. Very recently, taking the advantage of circulation of three distinct HBV genotypes within the population of eastern India, different aspects of HBV molecular epidemiology was studied that revealed very interesting results. In this study, the clinical significance of HBV genotypes, core promoter and precore mutations, possible routes of introduction of HBV genotype C in eastern India, the clinical implications of x gene variability, prevalence of the AFB 1 induced p53 gene codon 249 mutation, the transmission potentiality of HBV among asymptomatic/inactive or occult HBV carriers and the genetic variability of HBV persisting in the PBL was investigated. In this manuscript, the information available on the molecular epidemiology of HBV in India has been reviewed and the results of studies among the eastern Indian population have been summarised.

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          Most cited references77

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          TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer.

          Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the major risk factors include chronic infections with the hepatitis B (HBV) or C (HCV) virus, and exposure to dietary aflatoxin B(1) (AFB(1)) or alcohol consumption. Multiple genetic and epigenetic changes are involved in the molecular pathogenesis of HCC, for example, somatic mutations in the p53 tumor suppressor gene (TP53) and the activation of the WNT signal transduction pathway. AFB(1) frequently induces G:C to T:A transversions at the third base in codon 249 of TP53 and cooperates with HBV in causing p53 mutations in HCC. The detection of TP53 mutant DNA in plasma is a biomarker of both AFB(1) exposure and HCC risk. Chronic infection with HBV and HCV viruses, and oxyradical disorders including hemochromatosis, also generate reactive oxygen/nitrogen species that can both damage DNA and mutate cancer-related genes such as TP53. Certain mutant p53 proteins may exhibit a 'gain of oncogenic function'. The p53 biological network is a key responder to this oxidative and nitrosative stress. Depending on the extent of the DNA damage, p53 regulates the transcription of protective antioxidant genes and with extensive DNA damage, transactivates pro-oxidant genes that contribute to apoptosis. The X gene of HBV (HBx) is the most common open reading frame integrated into the host genome in HCC and the integrated HBx is frequently mutated. Mutant HBx proteins still retain their ability to bind to p53, and attenuate DNA repair and p53-mediated apoptosis. In summary, both viruses and chemicals are implicated in the etiology of TP53 mutations during the molecular pathogenesis of HCC.
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            Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes.

            The complete nucleotide sequences of the DNA of three hepatitis B virus (HBV) genomes of subtype adw, cloned from plasma samples of asymptomatic carriers living in the mainland and Okinawa Prefecture of Japan and Indonesia were determined. All three comprised 3215 bp and differed in sequence by only 3.9 to 5.6%. When these isolates were compared with the reported sequences of two HBV genomes of the same subtype derived from American carriers, however, the differences were greater (8.3 to 9.3% to an extent comparable with the nucleotide divergence between an HBV genome of subtype adw and that of a heterotypic subtype, such as adr, ayw or ayr. A total of 18 HBV genomes of various subtypes, including the three described here, 10 reported previously and five unpublished ones, were classified into four groups based on an inter-group divergence in nucleotide sequence of 8% or greater: group A (two adw genomes), group B (four adw), group C (three adw, four adr and one ayr) and group D (four ayw). Thus, the nine genomes of HBV subtype adw were distributed into three groups with considerably different sequences. These results indicate that the four major antigenically defined subtypes of envelope polypeptide do not reflect true genotypic variation of HBV. The fact that d to y, as well as w to r, subtypic change can be induced by an A----G point mutation at nucleotides 365 and 479 in the S gene, respectively, supports this view.
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              The enigmatic X gene of hepatitis B virus.

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                Author and article information

                Journal
                Virol J
                Virology Journal
                BioMed Central
                1743-422X
                2008
                19 December 2008
                : 5
                : 156
                Affiliations
                [1 ]ICMR Virus Unit Kolkata, Infectious Diseases & Beleghata General Hospital Campus, 57 Dr. Suresh Chandra Banerjee Road, Kolkata 700010, India
                Article
                1743-422X-5-156
                10.1186/1743-422X-5-156
                2640379
                19099581
                b61f0987-aef6-47f1-8bc6-48500540f1ea
                Copyright © 2008 Datta; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 December 2008
                : 19 December 2008
                Categories
                Review

                Microbiology & Virology
                Microbiology & Virology

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