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Open AccessArticle

Comprehensive Analysis of Hepatitis B Virus Promoter Region Mutations

1
Department of Microbiology, Immunology and Infectious Diseases, Cumming, School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
2
Alberta RNA Research & Training Institute, Department of Chemistry & Biochemistry, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada
3
Department of Ecosystem & Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
4
Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Calgary, AB T2N 4Z6, Canada
5
DiscoveryLab, Faculty of Medicine & Dentistry, Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2H7, Canada
*
Author to whom correspondence should be addressed.
Viruses 2018, 10(11), 603; https://doi.org/10.3390/v10110603
Received: 14 October 2018 / Revised: 27 October 2018 / Accepted: 31 October 2018 / Published: 1 November 2018
(This article belongs to the Special Issue CSV2018: The 2nd symposium of the Canadian Society for Virology (CSV))
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. View Full-Text
Keywords: Hepatitis B virus (HBV); cccDNA; basal core promoter; X promoter; single nucleotide polymorphisms; logo analyses; genotype alignments Hepatitis B virus (HBV); cccDNA; basal core promoter; X promoter; single nucleotide polymorphisms; logo analyses; genotype alignments
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MDPI and ACS Style

Meier-Stephenson, V.; Bremner, W.T.R.; Dalton, C.S.; Van Marle, G.; Coffin, C.S.; Patel, T.R. Comprehensive Analysis of Hepatitis B Virus Promoter Region Mutations. Viruses 2018, 10, 603.

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