Preprint Article Version 1 This version is not peer-reviewed

Comprehensive Analysis of Hepatitis B Virus Promoter Region Mutations

Version 1 : Received: 14 October 2018 / Approved: 15 October 2018 / Online: 15 October 2018 (13:03:06 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Viruses 2018, 10, 603
DOI: 10.3390/v10110603

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.

Subject Areas

hepatitis B virus (HBV); cccDNA; basal core promoter; X promoter; single nucleotide polymorphisms; logo analyses; genotype alignments

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