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Unique hepatitis B virus subgenotype in a primitive tribal community in eastern India.

ABSTRACT: Hepatitis B virus (HBV) strains isolated from members of the primitive Paharia ethnic community of Eastern India were studied to gain insight into the genetic diversity and evolution of the virus. The Paharia tribe has remained quite separate from the rest of the Indians and differs culturally, genetically, and linguistically from the mainstream East Indian population, whose HBV strains were previously characterized. Full-length HBV DNA was PCR amplified, cloned, and sequenced. Phylogenetic relationships between the tribal sequences and reference sequences from the mainstream population were assessed, and divergence times of subgenotypes of HBV genotype D were estimated. HBV was found in 2% of the Paharias participating in the study. A predominance of hepatitis B e antigen-negative infection (73%) was observed among the Paharias, and the genome sequences of the HBV strains exhibited relative homogeneity, with a very low prevalence of mutations. The novel feature of Paharia HBV was the exclusive presence of the D5 subgenotype, which was recently identified in Eastern India. Analysis of the four open reading frames (ORFs) of these tribal HBV D5 sequences and comparison with previously reported D1 to D7 sequences enabled the identification of 27 specific amino acid residues, including 6 unique ones, that could be considered D5 signatures. The estimated divergence times among subgenotypes D1 to D5 suggest that D5 was the first to diverge and hence is the most ancient of the D subgenotypes. The presence of a specific, ancient subgenotype of HBV within an ethnically primitive, endogamous population highlights the importance of studies of HBV genetics in well-separated human populations to understand viral transmission between communities and genome evolution.

SUBMITTER: Ghosh S

PROVIDER: S-EPMC3020822 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Unique hepatitis B virus subgenotype in a primitive tribal community in eastern India.

Ghosh Sumantra S Banerjee Priyanka P RoyChoudhury Arindam A Sarkar Sumanta S Ghosh Alip A Santra Amal A Banerjee Soma S Das Kausik K Dwibedi Bhagirathi B Kar Shantanu K SK Rao Vikas Gangadhar VG Bhat Jyothi T JT Singh Neeru N Chowdhury Abhijit A Datta Simanti S

Journal of clinical microbiology 20100915 11

Hepatitis B virus (HBV) strains isolated from members of the primitive Paharia ethnic community of Eastern India were studied to gain insight into the genetic diversity and evolution of the virus. The Paharia tribe has remained quite separate from the rest of the Indians and differs culturally, genetically, and linguistically from the mainstream East Indian population, whose HBV strains were previously characterized. Full-length HBV DNA was PCR amplified, cloned, and sequenced. Phylogenetic rela ...[more]

PMID: 20844228

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Project description:AimTo molecularly characterize hepatitis B virus (HBV) isolates from Kerala and to relate them to the clinical manifestation of infection.MethodsSera and clinical data were collected from 91 patients diagnosed with chronic HBV infection and HBV-related hepatocellular carcinoma (HCC). HBV from 44 HCC, 22 cirrhotic and 25 chronic hepatitis patients were genotyped by sequencing of the complete S region or by restriction fragment length polymorphism assays. The basic core promoter/precore region was sequenced. The complete surface DNA sequences were assembled and aligned manually, and then compared with the sequences of HBV of genotypes (A-J) from GenBank. The evolutionary history was inferred using the Neighbor-Joining method and the evolutionary distances computed using the Kimura 2-parameter method. Bootstrapping was performed using 1000 replicates. The TaqMan BS-1 probe was used to quantify HBV DNA at a lower detection limit of approximately 20 IU/mL. Continuous variables were compared using an independent Student's t test. The χ² test or Fisher's exact test was used to compare categorical variables. The differences were considered statistically significant at P < 0.05.ResultsIrrespective of disease status, the predominant genotype was A (72%); 95% belonging to subgenotype A1, followed by genotypes D (27%) and C (1%). HCC patients infected with subgenotype A1 were significantly younger than those infected with D. Mutation A1762T/G1764A was significantly associated with HCC in both genotypes A and D. Mutation G1862T was more frequent in subgenotype A1 (P < 0.0001), and in combination with A1762T/G1764A, it was significantly associated with HBV from HCC patients. Mutation C1766T/T1768A was significantly associated with genotype A (P = 0.05) and HCC (P = 0.03). The preS2 start codon M1T/I mutation was unique to genotype A strains (15.6%) from all disease groups and occurred at a higher frequency in isolates from HCC patients (P = 0.076). A higher frequency of preS deletion mutants (33.3%) was observed in genotype A from HCC compared with non-HCC patients, but did not reach statistical significance. The preS2:F22L mutation was found in genotypes A and D.ConclusionKerala is the first Indian state in which subgenotype A1 has been found to predominate in liver disease patients who developed HCC at a relatively young age.

Project description:Background/aimsHBV has been classified into ten genotypes (A-J) and multiple subgenotypes, some of which strongly influence disease outcome and their distribution also correlate with human migration. HBV infection is highly prevalent in India and its diverse population provides an excellent opportunity to study the distinctiveness of HBV, its evolution and disease biology in variegated ethnic groups. The North-East India, having international frontiers on three sides, is one of the most ethnically and linguistically diverse region of the country. Given the paucity of information on molecular epidemiology of HBV in this region, the study aimed to carry out an in-depth genetic characterization of HBV prevailing in North-East state of Tripura.MethodsFrom sera of chronically HBV infected patients biochemical/serological tests, HBV DNA quantification, PCR-amplification, sequencing of PreS/S or full-length HBV genomes were done. HBV genotype/subgenotype determination and sequence variability were assessed by MEGA5-software. The evolutionary divergence times of different HBV subgenotypes were estimated by DNAMLK/PHYLIP program while jpHMM method was used to detect any recombination event in HBV genomes.ResultsHBV genotypes D (89.5%), C (6.6%) and A (3.9%) were detected among chronic carriers. While all HBV/A and HBV/C isolates belonged to subgenotype-A1 and C1 respectively, five subgenotypes of HBV/D (D1-D5) were identified including the first detection of rare D4. These non-recombinant Indian D4 (IndD4) formed a distinct phylogenetic clade, had 2.7% nucleotide divergence and recent evolutionary radiation than other global D4. Ten unique amino acids and 9 novel nucleotide substitutions were identified as IndD4 signatures. All IndD4 carried T120 and R129 in ORF-S that may cause immune/vaccine/diagnostic escape and N128 in ORF-P, implicated as compensatory Lamivudine resistance mutation.ConclusionsIndD4 has potential to undermine vaccination programs or anti-viral therapy and its introduction to North-East India is believed to be linked with the settlement of ancient Tibeto-Burman migrants from East-Asia.

Project description:The focus of this study was the computational analysis of hepatitis B virus (HBV) genotype D subgenotype D1 in Pakistan, China, and India. In total, 54 complete genome sequences of HBV genotype D subgenotype D1 were downloaded from National Center for Biotechnology Information (NCBI). Of these, 6 complete genome sequences were from Pakistan, 14 were from China, and 34 were from India. Sequence alignment showed less than 4% divergence in these sequences. C and X genes showed divergence of less than 3%. Comparison over the S gene showed more than 97% similarity among the nucleotide sequences of genotype D subgenotype D1. The identity and similarity matrix of 54 nucleotide sequences of HBV genotype D subgenotype D1 from Pakistan, China, and India revealed more than 93% identity and 93% similarity. Phylogenetic analysis highlighted that complete genome isolates of HBV circulating in Pakistan had the closest evolutionary relationship with its neighboring countries China and India. China's (HQ833466) and Pakistan's (AB583680.1) isolates shared the same ancestor. Gene structure analysis showed that "P" gene exons were the longest, about three-fourth of the genome size, whereas gene "S" had the second longest coding regions with 2 exons and 1 intron. However, "C" and "X" genes had 1 smallest exon. X proteins had proven role in spreading of the HBV infection diseases. For HBx analysis, 1 X protein sequence of HBV genotype D subgenotype D1 belonging to each country was obtained. Homology models of the 3 X proteins generated using SWISS-MODEL revealed GMQE (Global Model Quality Estimation) = 0.1. Global and local quality estimate scores including Z-scores for Qualitative Model Energy Analysis (QMEAN) C-beta, all-atom, solvation, and torsion energy scores were similar indicating good quality, accuracy, and reliability of the predicted models. Three-dimensional (3D) visualization showed similar structures and Ramachandran plots showed a high percentage of protein residues into the favorable region for X protein models.

Project description:BackgroundTribal peoples are among the most marginalised groups worldwide. Evidence on birth outcomes in these groups is scant. We describe inequalities in Stillbirth Rate (SBR), Neonatal Mortality Rate (NMR), and uptake of maternal and newborn health services between tribal and less disadvantaged groups in eastern India, and examine the contribution of poverty and education to these inequalities.MethodsWe used data from a demographic surveillance system covering a 1 million population in Jharkhand State (March 2017 - August 2019) to describe SBR, NMR, and service uptake. We used logistic regression analysis combined with Stata's adjrr-command to estimate absolute and relative inequalities by caste/tribe (comparing Particularly Vulnerable Tribal Groups (PVTG) and other Scheduled Tribes (ST) with the less marginalised Other Backward Class (OBC)/none, using the Indian government classification), and by maternal education and household wealth.ResultsPVTGs had a higher NMR (59/1000) than OBC/none (31/1000) (rate ratio (RR): 1.92, 95%CI: 1.55-2.38). This was partly explained by wealth and education, but inequalities remained large after adjustment (adjusted RR: 1.59, 95%CI: 1.28-1.98). NMR was also higher among other STs (44/1000), but disparities were smaller (RR: 1.47, 95%CI: 1.23-1.75). There was a systematic gradient in NMR by maternal education and household wealth. SBRs were only higher in poorer groups (RRpoorest vs. least poor:1.56, 95%CI: 1.14-2.13). Uptake of facility-based services was low among PVTGs (e.g. institutional birth: 25% vs. 69% in OBC/none) and among poorer and less educated women. However, 65% of PVTG women with an institutional birth used a maternity vehicle vs. 34% among OBC/none. Visits from frontline workers (Accredited Social Health Activists [ASHAs]) were similar across groups, and ASHA accompaniment of institutional births was similar across caste/tribe groups, and higher among poorer and less educated women. Attendance in participatory women's groups was similar across caste/tribe groups, and somewhat higher among richer and better educated women.ConclusionsPVTGs are highly disadvantaged in terms of birth outcomes. Targeted interventions that reduce geographical barriers to facility-based care and address root causes of high poverty and low education in PVTGs are a priority. For population-level impact, they are to be combined with broader policies to reduce socio-economic mortality inequalities. Community-based interventions reach disadvantaged groups and have potential to reduce the mortality gap.

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Unique hepatitis B virus subgenotype in a primitive tribal community in eastern India.

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Unique hepatitis B virus subgenotype in a primitive tribal community in eastern India.

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