Abstract
A fragment of 600 bp of the gene which codes for the surface antigen of hepatitis B virus (HBV) was amplified and sequenced from patients who were born in five states of the Brazilian Amazon (Amazonas, Pará, Acre, Rondônia and Tocantins). A total of 44 sequences were used for the estimation of molecular genetic parameters and phylogenetic analyses. Compared with patients who were asymptomatic, those who had acute hepatitis and chronic liver disease had higher levels of genetic variability and higher rates of nucleotide substitutions. The analysis of transition and transversion substitutions showed that transition-type substitutions predominated. In chronic liver disease carriers, transversion-type substitutions showed phylogenetic saturation. In general, all of the analyses carried out in this study showed an association between patterns of changes in molecular genetic parameters and the stage of disease progression. Phylogenetic analysis using the HKY85 model of evolution identified 41 individuals as genotype A, suggesting its predominance in the Amazon region, one individual as genotype C, and one individual closely related to genotypes E and F.


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Arauz-Ruiz P, Norder H, Robertson BH, Magnius LO (2002) A new Amerindian genotype of hepatitis B virus revealed in Central America. J Gen Virol 83:2059–2073
Bowyer SM, Sim GM (2000) Relationships within and between genotypes of hepatitis B virus at points across the genome: footprints of recombination in certain isolates. J Gen Virol 81:379–392
Couroucé-Pauty AM, Plancon A, Soulier JP (1983) Distribution of HBsAg subtypes in the world. Vox Sang 44:197–211
Dane DS, Cameron CH, Briggs M (1970) Virus-like particles in serum of patients with Australia-antigen associated hepatitis. Lancet 1:695–698
Dumpis U, Holmes EC, Mendy M, Hill A, Thursz M, Hall A, Whittle H, Karayiannis P (2001) Transmission of hepatitis B virus infection in Gambia families revealed by phylogenetic analysis. J Hepatol 35:99–104
Fares M, Holmes E (2002) A revised evolutionary history of hepatitis B virus (HBV). J Mol Evol 54:807–814
Felsenstein J (2004) Inferring phylogenies. Sinauer Associates, Inc., Sunderland
Ganem D, Varmus HE (1987) The molecular biology of the hepatitis B viruses. Annu Rev Biochem 56:651–693
Gu X, Fu YX, Li WH (1995) Maximum likelihood estimation of the heterogeneity of substitution rate among nucleotide sites. Mol Biol Evol 12:546–557
Hall T (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98
Hannoun C, Horal P, Lindh M (2000) Long-term mutation rates in the hepatitis B virus genome. J Gen Virol 81:75–83
Hasegawa M, Kishino H, Yano TA (1985) Dating of the human–ape splitting by a molecular clock of mitochondrial DNA. J Mol Evol 22:160–174
Huelsenbeck JP, Ronquist FR (2001) MRBAYES: Bayesian inference of phylogeny. Bioinformatics 17:754–755
Kao JH, Chen PJ, Lai MY, Chen DS (2002) Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection. J Clin Microbiol 40:1207–1209
Karasawa T, Aizawa Y, Zeniya M, Kuramoto A, Shirasawa T, Toda G (1995) Genetic heterogeneity in the precore region of hepatitis B virus in hepatitis B e antigen-negative chronic hepatitis B patients: spontaneous seroconversion and interferon-induced seroconversion. J Med Virol 45:373–380
Kidd-Ljunggren K, Miyakawa Y, Kidd A (2002) Genetic variability in hepatitis B viruses. J Gen Virol 83:1267–1280
Kramvis A, Weitzmann L, Owiredu WKBA, Kew M (2002) Analysis of the complete genome of subgroup A′ hepatitis B virus isolates from South Africa. J Gen Virol 83:835–839
Lauder IJ, Lin HJ, Lau JYN, Siu TS, Lai CL (1993) The variability of the Hepatitis B virus genome: statistical analysis and biological implicationsNor. Mol Biol Evol 10:457–470
Li W-H (1997) Molecular evolution. Sinauer Associates, Sunderland
Mangnius LO, Norder H (1995) Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene. Intervirology 38:24–34
Moraes MTB, Gomes SA, Niel C (1996) Sequence analysis of pre-S/S gene of hepatitis B virus strains of genotypes A, D, and F isolated in Brazil. Arch Virol 141:01–07
Nakano T, Ling L, Hu X, Mizokami M, Orito E, Shapiro C, Hadler S, Robertson B (2001) Characterization of hepatitis B virus genotype among Yucpa indians in Venezuela. J Gen Virol 82:359–365
Niel C, Moraes MTB, Gaspar AMC, Yoshida CFT, Gomes AS (1994) Genetic diversity of hepatitis B virus strains isolated in Rio de Janeiro, Brazil. J Med Virol 44:180–186
Norder H, Courouce AM, Magnius LO (1994) Complete genomes, phylogenetic relatedness, and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes. Virology 198:489–503
Norder H, Couroucé A, Coursaget P, Echevarria JM, Lee S, Mushahwar IK, Robertson BH, Locarnini S, Magnius LO (2004) Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology 47:289–309
Okamoto H, Tsuda F, Sakugawa H, Sastrosoewignjo RI, Imai M, Miyakawa Y, Mayumi M (1988) Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes. J Gen Virol 69:2575–2583
Orito E, Mizokami M, Ina Y, Moriyama EN, Kameshima N, Yamamoto M, Gojobori T (1989) Host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences. Proc Natl Acad Sci USA 86:7059–7062
Osiowy C, Giles E, Tanaka Y, Mizokami M, Minuk G (2006) Molecular evolution of hepatitis B virus over 25 years. J Virol 80:10307–10314
Pan CQ, Zhang JX (2005) Natural history and clinical consequences of hepatitis B virus infection. Int J Med Sci 2:36–40
Posada D, Crandall KA (1998) MODELTEST: testing the model of DNA substitution. Bioinformatics 14:817–818
Starkman SE, MacDonald DM, Lewis JCM, Holmes EC, Simmonds P (2003) Geographic and species association of hepatitis B virus genotypes in non-human primates. Virology 314:381–393
Stuyver L, De Gendt S, Van Geyt C, Zoulim FZ, Fried M, Schinazi RF, Rossau R (2000) A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. J Gen Virol 81:67–74
Xia X, Xie Z (2001) DAMBE: data analysis in molecular biology and evolution. J Hered 92:371–373
Yang Z (1993) Maximum-likelihood estimation of phylogeny from DNA sequences when substitution rates differ over sites. Mol Biol Evol 10:1396–1401
Acknowledgments
This work was supported by Universidade Federal do Amazonas. The authors are grateful to Fundação de Medicina Tropical do Amazonas for technical assistance, samples and collaborations. Permission to collect blood samples have been granted by Comitê de Ética em Pesquisa da Fundação de Medicina Tropical do Amazonas (FMTAM) (License No. 158/99). We thank Tomas Hrbek and two anonymous referees for comments and suggestions on the manuscript. This work forms a portion of C.M.C.O. Ph D thesis at the Biotechnology program of Universidade Federal do Amazonas.
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de Oliveira, C.M., Farias, I.P., da Fonseca, J.C.F. et al. Phylogeny and molecular genetic parameters of different stages of hepatitis B virus infection in patients from the Brazilian Amazon. Arch Virol 153, 823–830 (2008). https://doi.org/10.1007/s00705-008-0053-6
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DOI: https://doi.org/10.1007/s00705-008-0053-6


