Comprehensive analysis of hepatitis B virus promoter region mutations
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Date
2018
Authors
Meier-Stephenson, Vanessa
Bremner, William T. R.
Dalton, Chimone S.
van Marle, Guido
Coffin, Carla S.
Patel, Trushar R.
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI
Abstract
Over 250 million people are infected chronically with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. HBV persists, due, in part, to its compact, stable minichromosome, the covalently-closed, circular DNA (cccDNA), which resides in the hepatocytes’ nuclei. Current therapies target downstream replication products, however, a true virological cure will require targeting the cccDNA. Finding targets on such a small, compact genome is challenging. For HBV, to remain replication-competent, it needs to maintain nucleotide fidelity in key regions, such as the promoter regions, to ensure that it can continue to utilize the necessary host proteins. HBVdb (HBV database) is a repository of HBV sequences spanning all genotypes (A–H) amplified from clinical samples, and hence implying an extensive collection of replication-competent viruses. Here, we analyzed the HBV sequences from HBVdb using bioinformatics tools to comprehensively assess the HBV core and X promoter regions amongst the nearly 70,000 HBV sequences for highly-conserved nucleotides and variant frequencies. Notably, there is a high degree of nucleotide conservation within specific segments of these promoter regions highlighting their importance in potential host protein-viral interactions and thus the virus’ viability. Such findings may have key implications for designing antivirals to target these areas.
Description
Open access article. Creative Commons Attribution 4.0 International license (CC BY 4.0) applies
Keywords
Hepatitis B virus (HBV) , cccDNA , Basal core promoter , X promoter , Single nucleotide polymorphisms , Logo analyses , Genotype alignments , Promoter regions
Citation
Meier-Stephenson, V., Bremner, W. T. R., Dalton, C. S., van Marle, G., Coffin, C. S., & Patel, T. R. (2018). Comprehensive analysis of hepatitis B virus promoter region mutations. Viruses, 10(11). Article 603. https://doi.org/10.3390/v10110603