Distribution of HBV genotypes, subgenotypes and HBsAg subtypes among chronically infected patients in Serbia
First Online: 06 August 2007 Received: 15 January 2007 Accepted: 12 June 2007 DOI:
Cite this article as: Lazarevic, I., Cupic, M., Delic, D. et al. Arch Virol (2007) 152: 2017. doi:10.1007/s00705-007-1031-0 Summary
Hepatitis B virus (HBV) has been classified into eight genotypes (some of them further divided into two or more subgenotypes) and nine HBsAg subtypes, distinctly distributed geographically. The aim of this study was to gain insight into the distribution of HBV genotypes, subgenotypes and HBsAg subtypes among HBV chronically infected patients in Serbia, since there were no previously published data on this subject. Eighty-nine plasma samples that gave a positive result in a nested PCR were included for genotype identification. Genotyping was performed by direct sequencing of the part of the S/pol gene, and the HBsAg subtype was deduced from the HBsAg sequence. Two HBV genotypes, A and D, were encountered in Serbia, with genotype D (D – 82%, A – 18%) and subgenotype D3 (47.9%) being prevalent. Genotype D isolates had three assigned subtypes (ayw2, ayw3, ayw4), with ayw2 found to be the most prevalent (ayw2 – 53.4%, ayw3 – 43.8%, ayw4 – 1.4%). Genotype A isolates belonged to the A2 subgenotype and the HBsAg subtype adw2, as expected for samples from European population. The results correspond to country’s geographical position, being in close proximity to the Mediterranean basin and on the main route between the Middle East and Central Europe.
References Amini-Bavil-Olyaee, S, Sarrami-Forooshani, R, Mahboudi, F, Sabahi, F, Adeli, A, Noorinayer, B, Azizi, M, Reza Zali, M 2005 Genotype characterization and phylogenetic analysis of hepatitis B virus isolates from Iranian patients J Med Virol 75 227 234 PubMed CrossRef Google Scholar Arauz-Ruiz, P, Norder, H, Robertson, BH, Magnius, LO 2002 Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America J Gen Virol 83 2059 2073 PubMed Google Scholar Bielawski, KP, Dybikowska, A, Lisowska-Charmuszko, U, Stalke, P, Gregorowicz, K, Trocha, H, et al. 2004 Distribution of HBV genotypes and mutants among hepatitis B infected patients from northern Poland Int J Mol Med 14 301 304 PubMed Google Scholar Bielawski, KP, Charmuszko, U, Dybikowska, A, Stalke, P, Podhajska, AJ 2006 Genetic variability of hepatitis B virus isolates in Poland J Med Virol 33 77 86 Google Scholar Bowyer, SM, Van Staden, L, Kew, MC, Sim, JGM 1997 A unique segment of the hepatitis B virus group A genotype identified in isolates from South Africa J Gen Virol 78 1719 1729 PubMed Google Scholar Bozdayi, AM, Aslan, N, Bozdayi, G, Turkyilmaz, AR, Sengezer, T, Wend, U, Erkan, O, Aydemir, F, Zakirhodjaev, S, Orucov, S, Bozkaya, H, Gerlich, W, Karayalcin, S, Yurdaydin, C, Uzunalimoglu, O 2004 Molecular epidemiology of hepatitis B, C and D viruses in Turkish patients Arch Virol 149 2115 2129 PubMed CrossRef Google Scholar Bozic, M 1998 Hepatitis B Delic, D Nikolic, P Bozic, M eds. Viral hepatitis Zavod za udzbenike i nastavna sredstva Belgrade 43 147 Google Scholar Carman, WF 1997 The clinical significance of surface antigen variants of hepatitis B virus J Viral Hepat 4 11 20 PubMed Google Scholar Courouce-Pauty, AM, Plancon, A, Soulier, JP 1983 Distribution of HBsAg subtypes in the world Vox Sang 35 197 211 CrossRef Google Scholar Echevarria, JM, Avellon, A, Magnius, LO 2005 Molecular epidemiology of hepatitis B virus in Spain: identification of viral genotypes and prediction of antigenic subtypes by limited sequencing J Med Virol 76 176 184 PubMed CrossRef Google Scholar Gandhe, SS, Chadha, MS, Arankalle, VA 2003 Hepatitis B virus genotypes and serotypes in Western India: lack of clinical significance J Med Virol 69 324 330 PubMed CrossRef Google Scholar Guldas, NS, Abacioglu, YH 2004 S-Gene sequences and genotype-related restriction sites in hepatitis B virus carriers in Turkey Infection 32 344 349 CrossRef Google Scholar Kao, JH 2002 Hepatitis B viral genotypes: clinical relevance and molecular characteristics J Gastroenterol Hepatol 17 643 650 PubMed CrossRef Google Scholar Kato, H, Fujiwara, K, Gish, RG, Sakugawa, H, Yoshizawa, H, Sugauchi, F, et al. 2005 Classifying genotype F of hepatitis B virus into F1 and F2 subtypes World J Gastroenterol 11 6295 6304 PubMed Google Scholar Kidd-Ljunggren, K, Miyakawa, Y, Kidd, AH 2002 Genetic variability in hepatitis B viruses J Gen Virol 83 1267 1280 PubMed Google Scholar Kimbi, GC, Kramvis, A, Kew, MC 2004 Distinctive sequence characteristics of subgenotype A1 isolates of hepatitis B virus from South Africa J Gen Virol 85 1211 1220 PubMed CrossRef Google Scholar Kramvis, A, Weitzmann, L, Owiredu, WK, Kew, MC 2002 Analysis of the complete genome of subgroup A’ hepatitis B virus isolates from South Africa J Gen Virol 83 835 839 PubMed Google Scholar Kumar, S, Tamura, K, Nei, M 2004 MEGA3: Integrated software for molecular evolutionary genetics analysis and sequence alignment Brief Bioinform 5 150 163 PubMed CrossRef Google Scholar Norder, H, Hammas, B, Lofdahl, S, Courouce, AM, Magnius, LO 1992 Comparison of the amino acid sequences of nine different serotypes of hepatitis B surface antigen and genomic classification of the corresponding hepatitis B virus J Gen Virol 73 1201 1208 PubMed Google Scholar Norder, H, Hammas, B, Lee, SD, Bile, K, Courouce, AM, Mushahwar, IK, Magnius, LO 1993 Genetic relatedness of hepatitis B viral strains of diverse geographical origin and natural variations in the primary structure of the surface antigen J Gen Virol 74 1341 1348 PubMed Google Scholar Norder, H, Courouce, AM, Magnius, LO 1994 Complete genome, phylogenetic relatedness, and structural protein of six strains of the hepatitis B virus, four of which represent two new genotypes Virology 198 489 503 PubMed CrossRef Google Scholar Norder, H, Courouce, AM, Coursaget, P, Echevarria, JM, Lee, SD, Mushahwar, IK, et al. 2004 Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes Intervirology 47 289 309 PubMed CrossRef Google Scholar 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 PubMed CrossRef Google Scholar Purdy, MA, Talekar, G, Swenson, P, Araujo, A, Fields, H 2007 A new algorithm for deduction of Hepatitis B surface antigen subtype determinants from the amino acid sequence Intervirology 50 45 51 PubMed CrossRef Google Scholar Roznovsky, L, Harrison, TJ, Fang, Z-L, Ling, R, Lochman, I, Orsagova, I, Pliskova, L 2000 Unusual hepatitis B surface antigen variation in a child immunised against hepatitis B J Med Virol 61 11 14 PubMed CrossRef Google Scholar Schaefer, S 2007 Hepatitis B virus taxonomy and hepatitis B virus genotypes World J Gastroenterol 13 14 21 PubMed Google Scholar Stuyver, L, De Gendt, S, Van Geyt, C, Zoulim, F, 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 PubMed Google Scholar Sugauchi, F, Kumada, H, Sakugawa, H, Komatsu, M, Niitsuma, H, Watanabe, H, et al. 2004 Two subtypes of genotype B (Ba and Bj) of hepatitis B virus in Japan Clin Infect Dis 38 1222 1228 PubMed CrossRef Google Scholar Sunbul, M, Leblebicioglu, H 2005 Distribution of hepatitis B virus genotypes in patients with chronic hepatitis B in Turkey World J Gastroenterol 11 1976 1980 PubMed Google Scholar Tabor, E 2006 Infections by hepatitis B surface antigen gene mutations in Europe and North America J Med Virol 78 S43 S47 PubMed CrossRef Google Scholar Tallo, T, Norder, H, Tefanova, V, Krispin, T, Priimagi, L, Mukomolov, S, et al. 2004 Hepatitis B virus genotype D strains from Estonia share sequence similarity with strains from Siberia and may specify ayw4 J Med Virol 74 221 227 PubMed CrossRef Google Scholar Weber, B 2005 Genetic variability of the S gene of hepatitis B virus: clinical and diagnostic impact J Clin Virol 32 102 112 PubMed CrossRef Google Scholar Zollner, B, Petersen, J, Schafer, P, Schroter, M, Laufs, R, Sterneck, M, Feucht, HH 2002 Subtype-dependent response of hepatitis B virus during the early phase of Lamivudine treatment Clin Infect Dis 34 1273 1277 PubMed CrossRef Google Scholar