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A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge?
BACKGROUND/AIMS: HBV 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 opport...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190083/ https://www.ncbi.nlm.nih.gov/pubmed/25295865 http://dx.doi.org/10.1371/journal.pone.0109425 |
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author | Banerjee, Priyanka Mondal, Rajiv Kumar Nandi, Madhuparna Ghosh, Sumantra Khatun, Mousumi Chakraborty, Nabendu Bhattacharya, Swatilekha RoyChoudhury, Arindam Banerjee, Soma Santra, Amal Sil, Samir Chowdhury, Abhijit Bhaumik, Pradip Datta, Simanti |
author_facet | Banerjee, Priyanka Mondal, Rajiv Kumar Nandi, Madhuparna Ghosh, Sumantra Khatun, Mousumi Chakraborty, Nabendu Bhattacharya, Swatilekha RoyChoudhury, Arindam Banerjee, Soma Santra, Amal Sil, Samir Chowdhury, Abhijit Bhaumik, Pradip Datta, Simanti |
author_sort | Banerjee, Priyanka |
collection | PubMed |
description | BACKGROUND/AIMS: HBV 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. METHODS: From 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. RESULTS: HBV 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 T(120) and R(129) in ORF-S that may cause immune/vaccine/diagnostic escape and N(128) in ORF-P, implicated as compensatory Lamivudine resistance mutation. CONCLUSIONS: IndD4 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. |
format | Online Article Text |
id | pubmed-4190083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41900832014-10-10 A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge? Banerjee, Priyanka Mondal, Rajiv Kumar Nandi, Madhuparna Ghosh, Sumantra Khatun, Mousumi Chakraborty, Nabendu Bhattacharya, Swatilekha RoyChoudhury, Arindam Banerjee, Soma Santra, Amal Sil, Samir Chowdhury, Abhijit Bhaumik, Pradip Datta, Simanti PLoS One Research Article BACKGROUND/AIMS: HBV 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. METHODS: From 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. RESULTS: HBV 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 T(120) and R(129) in ORF-S that may cause immune/vaccine/diagnostic escape and N(128) in ORF-P, implicated as compensatory Lamivudine resistance mutation. CONCLUSIONS: IndD4 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. Public Library of Science 2014-10-08 /pmc/articles/PMC4190083/ /pubmed/25295865 http://dx.doi.org/10.1371/journal.pone.0109425 Text en © 2014 Banerjee et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Banerjee, Priyanka Mondal, Rajiv Kumar Nandi, Madhuparna Ghosh, Sumantra Khatun, Mousumi Chakraborty, Nabendu Bhattacharya, Swatilekha RoyChoudhury, Arindam Banerjee, Soma Santra, Amal Sil, Samir Chowdhury, Abhijit Bhaumik, Pradip Datta, Simanti A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge? |
title | A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge? |
title_full | A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge? |
title_fullStr | A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge? |
title_full_unstemmed | A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge? |
title_short | A Rare HBV Subgenotype D4 with Unique Genomic Signatures Identified in North-Eastern India –An Emerging Clinical Challenge? |
title_sort | rare hbv subgenotype d4 with unique genomic signatures identified in north-eastern india –an emerging clinical challenge? |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190083/ https://www.ncbi.nlm.nih.gov/pubmed/25295865 http://dx.doi.org/10.1371/journal.pone.0109425 |
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