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World J Gastroenterol. Jun 28, 2014; 20(24): 7622-7634
Published online Jun 28, 2014. doi: 10.3748/wjg.v20.i24.7622
Enigmatic origin of hepatitis B virus: An ancient travelling companion or a recent encounter?
Gianguglielmo Zehender, Erika Ebranati, Elena Gabanelli, Chiara Sorrentino, Alessandra Lo Presti, Elisabetta Tanzi, Massimo Ciccozzi, Massimo Galli
Gianguglielmo Zehender, Erika Ebranati, Elena Gabanelli, Chiara Sorrentino, Massimo Galli, L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, 20157 Milan, Italy
Alessandra Lo Presti, Massimo Ciccozzi, Department of Infectious, Parasitic and Immunomediated Diseases, National Institute of Health, 00161 Rome, Italy
Elisabetta Tanzi, Department of Biomedical Sciences for Health, University of Milan, 20157 Milan, Italy
Author contributions: Zehender G, Tanzi E, Ciccozzi M and Galli M wrote the paper; Ebranati E, Gabanelli E, Sorrentino C and Lo Presti A made the analyses and prepared the figures.
Correspondence to: Gianguglielmo Zehender, PhD, Assistant Professor, L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Via GB Grassi 74, 20157 Milano, Italy. gianguglielmo.zehender@unimi.it
Telephone: +39-2-50319770 Fax: +39-2-50319768
Received: October 29, 2013
Revised: January 28, 2014
Accepted: March 12, 2014
Published online: June 28, 2014
Abstract

Hepatitis B virus (HBV) is the leading cause of liver disease and infects an estimated 240 million people worldwide. It is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral replication. The ten genotypes (A-J) that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic distribution. Genotypes A and D are ubiquitous and the most prevalent genotypes in Europe (mainly represented by subgenotypes D1-3 and A2); genotypes B and C are restricted to eastern Asia and Oceania; genotype E to central and western Africa; and genotypes H and F (classified into 4 subgenotypes) to Latin America and Alaska. This review summarises the data obtained by studying the global phylodynamics and phylogeography of HBV genotypes, particularly those concerning the origin and dispersion histories of genotypes A, D, E and F and their subgenotypes. The lack of any consensus concerning the HBV substitution rate and the conflicting data obtained using different calibration approaches make the time of origin and divergence of the various genotypes and subgenotypes largely uncertain. It is hypothesised that HBV evolutionary rates are time dependent, and that the changes depend on the main transmission routes of the genotypes and the dynamics of the infected populations.

Keywords: Hepatitis B virus genotypes and subgenotypes, Phylogeography, Population dynamics and epidemics, Molecular epidemiology, Hepatitis B virus phylodynamics

Core tip: This review describes the main evidence concerning the global phylodynamics and phylogeography of hepatitis B virus (HBV) genotypes and subgenotypes, concentrating particularly on the ubiquitous A and D, and the more restricted E and F genotypes. The lack of consensus on the HBV evolutionary rate make it difficult to reconstruct the timescale of the virus origin. In order to reconcile the possibility of a long evolution and the high evolutionary rate in recent populations, we propose the hypothesis that HBV evolutionary rates are time dependent, and are influenced by the different population dynamics of the viral genotypes.