Search Article Keyword:  

PubMed Submission Abstract PDF   Click Count: 8016 Download Count: 3543 

ISSN 1007-9327 CN 14-1219/R  World J Gastroenterol  2007 January 7;13(1):14-21

Hepatitis B virus taxonomy and hepatitis B virus genotypes

Stephan Schaefer

Stephan Schaefer, Abteilung für Virologie, Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universität Rostock, Schillingallee 70, D-18057 Rostock, Germany

Correspondence to: Stephan Schaefer, Abteilung für Virologie, Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universität Rostock Schillingallee 70, D-18057 Rostock, Germany.

Telephone: +49-381-4945920  Fax: +49-381-4945925

Received: 2006-09-01            Accepted: 2006-10-12



Hepatitis B virus (HBV) is a member of the hepadnavirus family. Hepadnaviruses can be found in both mammals (orthohepadnaviruses) and birds (avihepadnaviruses). The genetic variability of HBV is very high. There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV. Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties. In addition, recombination among HBV genotypes increases the variability of HBV. This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and, due to rapid progress in the field, updates several recent reviews on HBV genotypes and subgenotypes.


© 2007 The WJG Press. All rights reserved.


Key words: Orthohepadnavirus; Avihepadnavirus; Hepatitis B virus; Genotype, Subgenotype; Recombi-nation


Schaefer S. Hepatitis B virus taxonomy and hepatitis B virus genotypes. World J Gastroenterol 2007; 13(1): 14-21



Hepatitis B virus (HBV) is the prototype member of a steadily growing family of viruses called hepadnaviruses[1]. Hepadnaviruses can be found in both mammals (orthohepadnaviruses) and birds (avihepadnaviruses). HBV, the hepadnavirus infecting humans, is classified into eight genotypes today. HBV genotypes differ by at least 8%[2]. Since the first definition of the genotypes A, B, C and D[2], genotypes E[3], F[4], G[5] and H[6] have been detected. Due to the genetic diversity of HBV, numerous subgenotypes of HBV have been described[7] (Table 1). HBV subgenotypes differ by at least 4%[8].

HBV genotypes and most subgenotypes show a distinct geographic distribution. In Asia, where there is a high prevalence of HBV carriers, strong evidence suggests that HBV genotypes influence the course of disease. Several recent reviews have summarised knowledge on different aspects of HBV genotypes[7-12] and on hepadnaviruses that infect species other than homo sapiens[13-15]. This review will update recent developments in understanding HBV genotypes and taxonomy.



HBV is a partially double stranded virus that uses reverse transcriptase in its replication cycle. Thus, HBV is similar to many retroviruses found in animals and pararetroviruses in plants[16,17].

After cloning and sequencing the HBV genome[18], several related viruses were discovered in woodchucks (Marmota monax)[19], ground squirrels (Spermophilus beecheyi)[20] and pekin duck (Anas domesticus)[21]. Subsequently, numerous new viruses that are similar to HBV were found in mammals and birds and have been cloned (Tables 1 and 2). All these viruses are classified in the family of hepadnaviridae, including the genus orthohepdnavirus (mammals; Figure 1), and the genus avihepadnavirus (birds; Figure 2). In addition to the avihepadnaviruses listed in Table 2, five new hepadnaviruses were cloned from exotic duck and goose species; i.e., the Chiloe wigeon, mandarin duck, puna teal, Orinoco sheldgoose, and ashy-headed sheldgoose. Sequence comparisons revealed that 4 virus isolates were closely related to existing isolates of duck hepatitis B virus (DHBV), while the mandarin duck virus was closely related to Ross goose hepatitis B virus[22].

In chimpanzees, gorillas, orangutans and gibbons new putative members of hepadnaviridae were discovered and sequenced completely[14]. It is now widely accepted that primate hepadnaviruses are indigenous to their hosts. Because hepadnaviruses isolated from apes are grouped as HBV genotypes in phylogenetic analyses, it has been suggested that isolates from apes should be named following the nomenclature used for immune deficiency viruses[23] (Table 1), e.g. HBV found in chimpanzees should be called HBVcpz. With only 5% divergence from the chimpanzee HBV isolates, the HBV isolate from gorilla is categorized in the HBV genotype (Figure 3, unpublished results). Thus, three HBV genotypes from apes can now be differentiated. The chimpanzee and gorilla isolates from Africa are categorized as one genotype, i.e., HBVcpz. The isolates from the South-East-Asian apes, gibbon and orang-utan, are categorized into two genotypes, i.e., HBVgbn and HBVoru, respectively. These genotypes diverge by 8%. Within the gibbon genotype, distinct strains of HBV circulating in geographically separated populations have been described[24].

Avihepdnaviruses are the most distant relatives of HBV with a nucleic acid homology of only 40%. WHV and GSHV as mammalian hepadnaviruses are more closely related to HBV and differ by only 17%. Complete WHV and GSHV genomes from GenBank show a high degree of homology and only one genotype is listed[25-27]. However, using degenerate primers, several variant WHV isolates from wild-captured woodchucks were found that showed high divergence with sequencing of small parts of the genome[28]. DHBV has two genotypes, in contrast to WHV and GSHV, which have a narrow host range and geographical distribution[25,26], DHBV is found in different avian species with independent isolates in many countries around the world[29] (Figure 4).

Human HBV can be grouped into eight genotypes (based on more than 8% difference)[7,9-12]. Several attempts have been made to reconstruct the evolution of hepadnaviruses[30-34]. Estimating the rate of synonymous substitutions for HBV to be 4.57 × 10-5 per site per year, DHBV has been proposed to have diverged about 30000 years ago from a common ancestor while GSHV and WHV should have diverged about 10000 years ago from HBV and the HBV serotypes would be separated by about 3000 years[31]. However, as long as we are not able to accurately estimate the mutation rate of HBV over centuries or even millennia, it is not possible to calculate a time point for the separation of HBV genotypes or hepadnaviral species. 



HBV genotypes differ by more than 8%[2,3]. Phylogenetic analyses using alignments of whole genomes have shown that 8 genotypes, called A, B, C, D, E, F, G and H, of HBV can be distinguished[7,11,12,35] (Figure 1). In general, HBV isolates found in apes diverge similarly to HBV genotypes in phylogenetic analyses and have been named HBVcpz, -oru, -gor and -gbn for their host’s, i.e. chimpanzee, orang-utan, gorilla and gibbon, respectively (Table 1)[23]. However, as elucidated above, the isolate from gorillas is always categorized into the chimpanzee clade.

A prototypic HBV genome may have a length of 3215 nt, as found in HBV genotypes B, C, F and H. Due to deletions and insertions (Table 3), the other HBV genotypes differ slightly in length of genome (Table 3). Thus HBV genotype G with 3248 nt. is 66 nt longer than genotype D with 3182 bp.

Extensive phylogenetic analyses have shown that HBV genotypes can be further subdivided into subgenotypes (Table 4). HBV subgenotypes differ by at least 4%[8]. In genotypes A, B and C, epidemiological data show that the respective subgenotype pairs A1/A2 (formerly termed Aa/Ae)[36], B1/B2 (formerly Bj/Ba)[36] and C1/C2 (formerly Cs/Ce)[37-39] differ substantially in many virological and probably some clinical parameters. Subgenotypes also show distinct geographic distribution (Figure 3). However, this is not true for genotype D with subgenotypes D1, D2 and D3 being described as widespread in the world; e.g. D3 was found in Asia (East India)[40], South Africa[41] and Europe (Serbia) (Stanojevic et al, unpublished results).

Except for genotype E and G, all HBV genotypes can be divided into subgenotypes. The absence of subgenotypes in HBV genotype E has been assumed to be the consequence of a recent genesis for genotype E[42-45]. Furthermore, genotype E is not present in Americans of African origin from Venezuela and Brazil[46,47]. The case for HBV genotype G appears to be less clear. Genotype G was originally found in the USA, France[5] and Germany[48]. Later, partial sequencing of HBV genes pointed to a high prevalence of HBV genotype G in Mexico[49]. Nevertheless, the geographic origin of HBV genotype G remains unknown[50]. To date only a limited number of complete HBV genotype G sequences have been deposited in GenBank that are not classified into subgenotypes.



Double infections with two different HBV genotypes have been known since typing was done serologically[51,52]. Subsequently, evidence of super infection with HBV isolates of the same or different genotype was described in chronic HBV patients[53]. Super infection was accompanied by acute exacerbation of the chronic disease. Additional observations came from patients treated with interferon. Before treatment, HBV genotype A was prevalent. After treatment and relapse, a switch of the genotype to HBV genotype D was described[54,55].

Using different methods for genotyping, several reports described high rates of double infection with two different HBV genotypes in all parts of the world. Using these methods double infections have been found in 4.4%[56], 10.9%[57], 12.5%[58], 14.1% (Kirschberg et al, unpublished results), 17.3%[59] and 17.5%[60] of HBV infected patients. Even triple infections with HBV of genotype A, B and C have been described in 0.9% of HBV infected intravenous drug users[60].

Infection with HBV of genotype G seems to be associated very often with an infection of HBV genotype A[61]. This was found in 4 individuals from the USA and in one patient from France[62].

Coinfection with two different HBV genotypes in one patient may lead to an exchange of genetic material between the two strains. However, with current knowledge of HBV replication, the mechanism for this supposed recombination remains enigmatic. No mechanism can be envisioned that would allow an exchange of genetic material between two hepadnaviral genomes at the level of transcription. Nevertheless, numerous authors described changes in the genome of HBV that appear to be the consequences of a recombinatorial event (Figure 5 and Table 5).   

Two recent works have comprehensively analysed the prevalence of events in the HBV genome that are reminiscent of recombinations[63,64]. About 87% of the putative recombinants were B/C (120) and A/D (29) hybrids. The other recombinants comprised A/B/C, A/C, A/E, A/G, C/D, C/F, C/G, C/U (U for unknown genotype) and B/C/U hybrids. Genotypes A and C showed a higher recombination tendency than did other genotypes. The results also demonstrated region priority and breakpoint hot spots in the intergenotype recombination. Recombination breakpoints were found to be concentrated mainly in the vicinity of the DR1 region (nt 1640-1900), the preS1/S2 region (nt 3150-100), the 3’-end of the Core gene (nt 2330-2450) and the 3’-end of the Surface gene (nt 650-830)[63,64].

Recombination events between human and chim-panzee[65]or gibbon[63] HBV sequences have also been described. Discrepant genotyping results from different parts of the genome are indicative of a recombination between genotype A and F[66]. Even mosaic genomes with sequences derived from three different genotypes have been described[59,64].

Some recombinants among HBV genotypes have become the dominant subgenotype prevalent in certain geographic regions. Recombination between genotypes B and C has led to the generation of two different strains with distinct geographic distribution[67]. Strains of genotype B without recombination are found in Japan (subgenotype B1), whereas strains with recombination between genotype B and C are found throughout Asia (subgenotype B2), sparing Japan[67]. Recombinants between HBV genotypes C and D are the leading HBV subgenotype in Tibet[68-70].

It remains open for discussion whether the observed exchanges are the consequence of direct genetic recombination taking place between two HBV strains or if they are the consequence of fast adaptation of HBV to a certain genetic and immunologic environment in different human populations in the world. The high replication capacity of HBV with a release of up to 1013 viral particles per day[71,72] and the high error rate of the viral polymerase, lead to the production of HBV genomes with all possible single mutations and double mutations of every nucleotide of the HBV genome every day[72]. Thus, a fast adaptation of HBV to a new environment is also a possibility.

A hypothetical mosaicism of the HBV genome has already been proposed by Bowyer and Sim[73]. This work and later works described most HBV genotypes as a modular genome[63] that represents a mixture of small segments coming from many different HBV genotypes. If we expand on this observation, the HBV genome may be made up of a number of allelic modules with different properties; e.g. different binding sites for transcription factors or antigenic epitopes. Thus, a certain combination of these modules would make up an HBV genotype. The findings of Fischer et al are in support of this speculation. The authors described genotype specific activation or repression of HBV enhancer II, preCore-pregenomic promoter by the transcription factor COUP-TF1[74].



HBV has been recognised as a prototype member of a family of viruses infecting mammals and birds. Due to its high replication capacity and the high error rate of the viral reverse transcriptase, HBV is able to adapt to the host’s
environment. This adaptation has led to the emergence of eight genotypes in humans and three closely related genotypes in apes. The human genotypes have further diverged into at least 24 subgenotypes, with certainly many more to come, and a plethora of recombinants. From the analysis of recombinants there are indications that at least one more genotype remains to be detected.



1      Mason WS, Burrell CJ, Casey J, Gerlich WH, Howard CR, Kann M, Newbold J, Schaefer S, Taylor JM, Will H
        Hepadnaviridae. in: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA (eds). Virus Taxonomy. Eighth Report of
        the International Committee on Taxonomy of Viruses. Amsterdam: Elsevier, 2005

2      Okamoto H, Tsuda F, Sakugawa H, Sastrosewinjo RI, Imal M, Miyakawa Y, Mayumi M. Typing hepatitis B virus by
        homology in nucleotide sequence: comparison of surface antigen subtypes. J Gen Virol 1988;
69: 2575-2583    

3      Norder H, Courouce AM, Magnius LO. Complete genomes, phylogenetic relatedness, and structural proteins of six
        strains of the hepatitis B virus, four of which represent two new genotypes. Virology 1994; 198: 489-503   PubMed

4      Naumann H, Schaefer S, Yoshida CF, Gaspar AM, Repp R, Gerlich WH. Identification of a new hepatitis B virus (HBV)
        genotype from Brazil that expresses HBV surface antigen subtype adw4. J Gen Virol 1993; 74 (Pt 8): 1627-1632

5      Stuyver L, De Gendt S, Van Geyt C, Zoulim F, Fried M, Schinazi RF, Rossau R. A new genotype of hepatitis B virus:
        complete genome and phylogenetic relatedness. J Gen Virol 2000; 81: 67-74   PubMed

6      Arauz-Ruiz P, Norder H, Robertson BH, Magnius LO. Genotype H: a new Amerindian genotype of hepatitis B virus
        revealed in Central America. J Gen Virol 2002; 83: 2059-2073   PubMed

7      Norder H, Couroucé A-M, Coursaget P, Echevarria JM, Leef S-D, Mushahwar IK, Robertson BH, Locarnini S, Magnius LO.
        Genetic Diversity of Hepatitis B Virus Strains Derived Worldwide: Genotypes, Subgenotypes, and HBsAg Subtypes.
        Intervirology 2004;
47: 289-309   

8      Kramvis A, Kew MC. Relationship of genotypes of hepatitis B virus to mutations, disease progression and response to
        antiviral therapy. J Viral Hepat 2005; 12: 456-464   PubMed

9      Chu CJ, Lok AS. Clinical significance of hepatitis B virus genotypes. Hepatology 2002; 35: 1274-1276   PubMed

10    Kramvis A, Kew M, Francois G. Hepatitis B virus genotypes. Vaccine 2005; 23: 2409-2423   PubMed

11    Miyakawa Y, Mizokami M. Classifying hepatitis B virus genotypes. Intervirology 2003; 46: 329-338   PubMed

12    Schaefer S. Hepatitis B Virus-Significance of Genotypes. J Viral Hepat 2005; 12: 111-124   

13    Schaefer S, Tolle T, Lottmann S, Gerlich W. Animal Models and Experimental Systems in Hepatitis B Virus Research. in:
        Koshy R, Caselmann W (eds). Hepatitis B Virus: Molecular Mechanisms in Disease and Novel Strategies for Therapy.
        London: Imperial College Press, 1998
: 51-74 

14    Robertson BH, Margolis HS. Primate hepatitis B viruses - genetic diversity, geography and evolution. Rev Med Virol
        2002; 12: 133-141   PubMed

15    Burda MR, Gunther S, Dandri M, Will H, Petersen J. Structural and functional heterogeneity of naturally occurring
        hepatitis B virus variants. Antiviral Res 2001; 52: 125-138   PubMed

16    Abravaya K, Huff J, Marshall R, Merchant B, Mullen C, Schneider G, Robinson J. Molecular beacons as diagnostic tools:
        technology and applications. Clin Chem Lab Med 2003; 41: 468-474   PubMed

17    Li MD, Bronson DL, Lemke TD, Faras AJ. Phylogenetic analyses of 55 retroelements on the basis of the nucleotide and
        product amino acid sequences of the pol gene. Mol Biol Evol 1995; 12: 657-670   PubMed

18    Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype
        ayw) cloned in E. coli. Nature 1979; 281: 646-650   PubMed

19    Summers J, Smolec JM, Snyder R. A virus similar to human hepatitis B virus associated with hepatitis and hepatoma in
        woodchucks. Proc Natl Acad Sci USA 1978;
75: 4533-4537   

20    Marion PL, Oshiro LS, Regnery DC, Scullard GH, Robinson WS. A virus in Beechey ground squirrels that is related to
        hepatitis B virus of humans. Proc Natl Acad Sci USA 1980;
77: 2941-2945   

21    Mason WS, Seal G, Summers J. Virus of Pekin ducks with structural and biological relatedness to human hepatitis B
        virus. J Virol 1980;
36: 829-836     

22    Guo H, Mason WS, Aldrich CE, Saputelli JR, Miller DS, Jilbert AR, Newbold JE. Identification and characterization of
        avihepadnaviruses isolated from exotic anseriformes maintained in captivity. J Virol 2005; 79: 2729-2742   PubMed

23    Bartholomeusz A, Schaefer S. Hepatitis B virus genotypes: comparison of genotyping methods. Rev Med Virol 2004;
        14: 3-16   PubMed

24    Sall AA, Starkman S, Reynes JM, Lay S, Nhim T, Hunt M, Marx N, Simmonds P. Frequent infection of Hylobates pileatus
        (pileated gibbon) with species-associated variants of hepatitis B virus in Cambodia. J Gen Virol 2005; 86: 333-337


25    Marion PL Ground Squirrel Hepatitis Virus. in: MacLachlan A (ed). Molecular Biology of the Hepatitis B Virus. Boca
        Raton: CRC Press, 1991
: 39-51  

26    Paronetto F, Tennant BC. Woodchuck hepatitis virus infection: a model of human hepatic diseases and hepatocellular
        carcinoma. Prog Liver Dis 1990;
9: 463-483   

27    Roggendorf M, Tolle TK. Woodchuck: An Animal Model for Hepatitis B Virus Infection in Man. Intervirology 1995; 38:

28    Huang Z, Buckwold VE. A TaqMan PCR assay using degenerate primers for the quantitative detection of woodchuck
        hepatitis virus DNA of multiple genotypes. Mol Cell Probes 2005; 19: 282-289   PubMed

29    Schödel F, Weimer T, Fernholz D, Schneider R, Sprengel R, Wildner G, Will H The Biology of Avian Hepatitis B Viruses.
        in: MacLachlan A (ed). Molecular Biology of the Hepatitis B Virus. Boca Raton: CRC Press, 1991: 53-80

30    Bollyky PL, Holmes EC. Reconstructing the complex evolutionary history of hepatitis B virus. J Mol Evol 1999; 49: 130-
        141   PubMed

31    Orito E, Mizokami M, Ina Y, Moriyama EN, Kameshima N, Yamamoto M, Gojobori T. Host-independent evolution and a
        genetic classification of the hepadnavirus family based on nucleotide sequences. Proc Natl Acad Sci USA 1989;
        7059-7062   PubMed

32    Simmonds P. The origin and evolution of hepatitis viruses in humans. J Gen Virol 2001; 82: 693-712   PubMed

33    Simmonds P. Reconstructing the origins of human hepatitis viruses. Philos Trans R Soc Lond B Biol Sci 2001; 356:
        1013-1026   PubMed

34    Fares MA, Holmes EC. A revised evolutionary history of hepatitis B virus (HBV). J Mol Evol 2002; 54: 807-814   PubMed

35    Chu CJ, Hussain M, Lok AS. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with
        hepatitis B virus genotype C. Gastroenterology 2002;
122: 1756-1762   PubMed

36    Sugauchi F, Kumada H, Acharya SA, Shrestha SM, Gamutan MT, Khan M, Gish RG, Tanaka Y, Kato T, Orito E, Ueda R,
        Miyakawa Y, Mizokami M. Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B
        virus genotype A. J Gen Virol 2004;
85: 811-820   PubMed

37    Chan HL, Tsui SK, Tse CH, Ng EY, Au TC, Yuen L, Bartholomeusz A, Leung KS, Lee KH, Locarnini S, Sung JJ.
        Epidemiological and virological characteristics of 2 subgroups of hepatitis B virus genotype C. J Infect Dis 2005;
        2022-2032   PubMed

38    Huy TT, Ushijima H, Quang VX, Win KM, Luengrojanakul P, Kikuchi K, Sata T, Abe K. Genotype C of hepatitis B virus can
        be classified into at least two subgroups. J Gen Virol 2004;
85: 283-292   PubMed

39    Tanaka Y, Orito E, Yuen MF, Mukaide M, Sugauchi F, Ito K, Ozasa A, Sakamoto T, Kurbanov F, Lai CL, Mizokami M. Two
        subtypes (subgenotypes) of hepatitis B virus genotype C: A novel subtyping assay based on restriction fragment length
        polymorphism. Hepatol Res 2005;
33: 216-224   PubMed

40    Banerjee A, Kurbanov F, Datta S, Chandra PK, Tanaka Y, Mizokami M, Chakravarty R. Phylogenetic relatedness and
        genetic diversity of hepatitis B virus isolates in Eastern India. J Med Virol 2006;
78: 1164-1174   PubMed

41    Kimbi GC, Kramvis A, Kew MC. Distinctive sequence characteristics of subgenotype A1 isolates of hepatitis B virus from
        South Africa. J Gen Virol 2004;
85: 1211-1220   PubMed

42    Fujiwara K, Tanaka Y, Orito E, Ohno T, Kato T, Sugihara K, Hasegawa I, Sakurai M, Ito K, Ozasa A, Sakamoto Y, Arita I,
        El-Gohary A, Benoit A, Ogoundele-Akplogan SI, Yoshihara N, Ueda R, Mizokami M. Distribution of HBV genotypes among
        HBV carriers in Benin:phylogenetic analysis and virological characteristics of HBV genotype E. World J Gastroenterol
11: 6410-6415   PubMed

43    Huy TT, Ishikawa K, Ampofo W, Izumi T, Nakajima A, Ansah J, Tetteh JO, Nii-Trebi N, Aidoo S, Ofori-Adjei D, Sata T,
        Ushijima H, Abe K. Characteristics of hepatitis B virus in Ghana: full length genome sequences indicate the endemicity of
        genotype E in West Africa. J Med Virol 2006;
78: 178-184   PubMed  

44    Kramvis A, Restorp K, Norder H, Botha JF, Magnius LO, Kew MC. Full genome analysis of hepatitis B virus genotype E
        strains from South-Western Africa and Madagascar reveals low genetic variability. J Med Virol 2005;
77: 47-52


45    Mulders MN, Venard V, Njayou M, Edorh AP, Bola Oyefolu AO, Kehinde MO, Muyembe Tamfum JJ, Nebie YK, Maiga I,
        Ammerlaan W, Fack F, Omilabu SA, Le Faou A, Muller CP. Low genetic diversity despite hyperendemicity of hepatitis B
        virus genotype E throughout West Africa. J Infect Dis 2004;
190: 400-408   PubMed

46    Motta-Castro AR, Martins RM, Yoshida CF, Teles SA, Paniago AM, Lima KM, Gomes SA. Hepatitis B virus infection in
        isolated Afro-Brazilian communities. J Med Virol 2005;
77: 188-193   PubMed

47    Quintero A, Martinez D, Alarcon De Noya B, Costagliola A, Urbina L, Gonzalez N, Liprandi F, Castro De Guerra D, Pujol
        FH. Molecular epidemiology of hepatitis B virus in Afro-Venezuelan populations. Arch Virol 2002; 147: 1829-1836


48    Vieth S, Manegold C, Drosten C, Nippraschk T, Gunther S. Sequence and phylogenetic analysis of hepatitis B virus
        genotype G isolated in Germany. Virus Genes 2002;
24: 153-156   PubMed

49    Sanchez LV, Maldonado M, Bastidas-Ramirez BE, Norder H, Panduro A. Genotypes and S-gene variability of Mexican
        hepatitis B virus strains. J Med Virol 2002;
68: 24-32   PubMed

50    Lindh M. HBV genotype G-an odd genotype of unknown origin. J Clin Virol 2005; 34: 315-316   PubMed

51    Hess G, Arnold W, Koesters W, Biswas R, Hutteroth TH, zum Buschenfelde KH. Simultaneous presence of HBsAg and
        anti-HBs in the serum of different subtypes (serological and immunofluorescent studies). Z Immunitatsforsch Immunobiol
        1977; 153: 143-151   PubMed

52    Tabor E, Gerety RJ, Smallwood LA, Barker LF. Coincident hepatitis B surface antigen and antibodies of different subtypes
        in human serum. J Immunol 1977;
118: 369-370   PubMed

53    Kao JH, Chen PJ, Lai MY, Chen DS. Acute exacerbations of chronic hepatitis B are rarely associated with superinfection
        of hepatitis B virus. Hepatology 2001;
34: 817-823   PubMed

54    Gerner PR, Friedt M, Oettinger R, Lausch E, Wirth S. The hepatitis B virus seroconversion to anti-HBe is frequently
        associated with HBV genotype changes and selection of preS2-defective particles in chronically infected children.
        Virology 1998;
245: 163-172   PubMed

55    Hannoun C, Krogsgaard K, Horal P, Lindh M, Group tIT. Genotype Mixtures of Hepatitis B Virus in Patients Treated with
        Interferon. J Infect Dis 2002;
186: 752-759   

56    Ding X, Gu H, Zhong ZH, Zilong X, Tran HT, Iwaki Y, Li TC, Sata T, Abe K. Molecular epidemiology of hepatitis viruses
        and genotypic distribution of hepatitis B and C viruses in Harbin, China. Jpn J Infect Dis 2003;
56: 19-22   PubMed

57    Kato H, Orito E, Sugauchi F, Ueda R, Koshizaka T, Yanaka S, Gish RG, Kurbanov F, Ruzibakiev R, Kramvis A, Kew MC,
        Ahmad N, Khan M, Usuda S, Miyakawa Y, Mizokami M. Frequent coinfection with hepatitis B virus strains of distinct
        genotypes detected by hybridization with type-specific probes immobilized on a solid-phase support. J Virol Methods
110: 29-35   PubMed

58    Osiowy C, Giles E. Evaluation of the INNO-LiPA HBV genotyping assay for determination of hepatitis B virus genotype. J
        Clin Microbiol 2003;
41: 5473-5477   PubMed

59    Olinger CM, Venard V, Njayou M, Oyefolu AO, Maiga I, Kemp AJ, Omilabu SA, le Faou A, Muller CP. Phylogenetic
        analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections
        and recombinations. J Gen Virol 2006;
87: 1163-1173   PubMed

60    Chen BF, Kao JH, Liu CJ, Chen DS, Chen PJ. Genotypic dominance and novel recombinations in HBV genotype B and C co-
        infected intravenous drug users. J Med Virol 2004;
73: 13-22   PubMed

61    Kato H, Orito E, Gish RG, Bzowej N, Newsom M, Sugauchi F, Suzuki S, Ueda R, Miyakawa Y, Mizokami M. Hepatitis B e
        antigen in sera from individuals infected with hepatitis B virus of genotype G. Hepatology 2002;
35: 922-929   PubMed

62    Kremsdorf D, Garreau F, Capel F, Petit MA, Bréchot C. In vivo selection of a hepatitis B virus mutant with abnormal viral
        protein expression. J Gen Virol 1996;
77: 929-939  

63    Simmonds P, Midgley S. Recombination in the genesis and evolution of hepatitis B virus genotypes. J Virol 2005; 79:
        15467-15476   PubMed

64    Yang J, Xing K, Deng R, Wang J, Wang X. Identification of Hepatitis B virus putative intergenotype recombinants by using
        fragment typing. J Gen Virol 2006;
87: 2203-2215   PubMed

65    Magiorkinis EN, Magiorkinis GN, Paraskevis DN, Hatzakis AE. Re-analysis of a human hepatitis B virus (HBV) isolate from
        an East African wild born Pan troglodytes schweinfurthii: evidence for interspecies recombination between HBV infecting
        chimpanzee and human. Gene 2005;
349: 165-171   PubMed

66    Gutierrez C, Devesa M, Loureiro CL, Leon G, Liprandi F, Pujol FH. Molecular and serological evaluation of surface
        antigen negative hepatitis B virus infection in blood donors from Venezuela. J Med Virol 2004;
73: 200-207   PubMed

67    Sugauchi F, Orito E, Ichida T, Kato H, Sakugawa H, Kakumu S, Ishida T, Chutaputti A, Lai CL, Ueda R, Miyakawa Y,
        Mizokami M. Hepatitis B virus of genotype B with or without recombination with genotype C over the precore region plus
        the core gene.
J Virol 2002; 76: 5985-5992   PubMed

68    Cui C, Shi J, Hui L, Xi H, Zhuoma, Quni, Tsedan, Hu G. The dominant hepatitis B virus genotype identified in Tibet is a
        C/D hybrid. J Gen Virol 2002;
83: 2773-2777   

69    Wang Z, Liu Z, Zeng G, Wen S, Qi Y, Ma S, Naoumov NV, Hou J. A new intertype recombinant between genotypes C and
        D of hepatitis B virus identified in China. J Gen Virol 2005;
86: 985-990   PubMed

70    Zeng G, Wang Z, Wen S, Jiang J, Wang L, Cheng J, Tan D, Xiao F, Ma S, Li W, Luo K, Naoumov NV, Hou J. Geographic
        distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China. J Viral Hepat 2005;
12: 609-617


71    Nowak MA, Bonhoeffer S, Hill AM, Boehme R, Thomas HC, McDade H. Viral dynamics in hepatitis B virus infection. Proc
        Natl Acad Sci USA 1996;
93: 4398-4402   

72    Brechtbuehl K, Whalley SA, Dusheiko GM, Saunders NA. A rapid real-time quantitative polymerase chain reaction for
        hepatitis B virus. J Virol Methods 2001;
93: 105-113   PubMed

73    Bowyer SM, Sim JG. Relationships within and between genotypes of hepatitis B virus at points across the genome:
        footprints of recombination in certain isolates. J Gen Virol 2000;
81: 379-392   PubMed

74    Fischer SF, Schmidt K, Fiedler N, Glebe D, Schuttler C, Sun J, Gerlich WH, Repp R, Schaefer S. Genotype-dependent
        activation or repression of HBV enhancer II by transcription factor COUP-TF1. World J Gastroenterol 2006; 12: 6054-
        6058   PubMed

75    Dane DS, Cameron CH, Briggs M. Virus-like particles in serum of patients with Australia-antigen- associated hepatitis.
        Lancet 1970;
1: 695-698   

76    Vaudin M, Wolstenholme AJ, Tsiquaye KN, Zuckerman AJ, Harrison TJ. The complete nucleotide sequence of the
        genome of a hepatitis B virus isolated from a naturally infected chimpanzee. J Gen Virol 1988;
69: 1383-1389   

77    Norder H, Ebert JW, Fields HA, Mushahwar IK, Magnius LO. Complete sequencing of a gibbon hepatitis B virus genome
        reveals a unique genotype distantly related to the chimpanzee hepatitis B virus. Virology 1996;
218: 214-223   PubMed

78    Warren KS, Heeney JL, Swan RA, Heriyanto, Verschoor EJ. A new group of hepadnaviruses naturally infecting
        orangutans (Pongo pygmaeus). J Virol 1999;
73: 7860-7865   PubMed

79    Grethe S, Heckel JO, Rietschel W, Hufert FT. Molecular epidemiology of hepatitis B virus variants in nonhuman primates.
        J. Virol. 2000;
74: 5377- 5381     

80    Lanford RE, Chavez D, Brasky KM, Burns RB 3rd, Rico-Hesse R. Isolation of a hepadnavirus from the woolly monkey, a
        New World primate. Proc Natl Acad Sci USA 1998; 95: 5757-5761   PubMed

81    Testut P, Renard CA, Terradillos O, Vitvitski-Trépo L, Tekaia F, Degott C, Blake J, Boyer B, Buendia MA. A new
        hepadnavirus endemic in arctic ground squirrels in Alaska. J Virol 1996;
70: 4210-4219   

82    Li L, Dixon RJ, Gu X, Newbold JE: Comparison of the sequences of the Grey Teal, Maned Duck and Duck Hepatitis B
        Viruses. In The molecular biology of Hepatitis B Virus. University of California San Diego, 1998: 13

83    Sprengel R, Kaleta EF, Will H. Isolation and characterization of a hepatitis B virus endemic in herons. J Virol 1988; 62:

84    Chang SF, Netter HJ, Bruns M, Schneider R, Fröhlich K, Will H. A new avian hepadnavirus infecting snow geese (Anser
        caerulescens) produces a significant fraction of virions containing single-stranded DNA. Virology 1999;
262: 39-54

85    Pult I, Netter HJ, Fröhlich K, Kaleta EF, Will H: Identification, structural and functional analysis of a new avian
        Hepadnavirus from storks (STHBV). In The molecular biology of Hepatitis B Virus. University of California San Diego,
        1998: 2

86    Prassolov A, Hohenberg H, Kalinina T, Schneider C, Cova L, Krone O, Frolich K, Will H, Sirma H. New hepatitis B virus
        of cranes that has an unexpected broad host range. J Virol 2003;
77: 1964-1976   PubMed

87    Kramvis A, Weitzmann L, Owiredu WK, Kew MC. Analysis of the complete genome of subgroup A’ hepatitis B virus
        isolates from South Africa. J Gen Virol 2002;
83: 835-839   PubMed

88    Kurbanov F, Tanaka Y, Fujiwara K, Sugauchi F, Mbanya D, Zekeng L, Ndembi N, Ngansop C, Kaptue L, Miura T, Ido E,
        Hayami M, Ichimura H, Mizokami M. A new subtype (subgenotype) Ac (A3) of hepatitis B virus and recombination
        between genotypes A and E in Cameroon. J Gen Virol 2005;
86: 2047-2056   PubMed

89    Makuwa M, Souquiere S, Telfer P, Apetrei C, Vray M, Bedjabaga I, Mouinga-Ondeme A, Onanga R, Marx PA, Kazanji M,
        Roques P, Simon F. Identification of hepatitis B virus subgenotype A3 in rural Gabon. J Med Virol 2006;
78: 1175-1184


90    Sugauchi F, Orito E, Ichida T, Kato H, Sakugawa H, Kakumu S, Ishida T, Chutaputti A, Lai CL, Gish RG, Ueda R,
        Miyakawa Y, Mizokami M. Epidemiologic and virologic characteristics of hepatitis B virus genotype B having the
        recombination with genotype C. Gastroenterology 2003; 124: 925-932   PubMed  

91    Nagasaki F, Niitsuma H, Cervantes JG, Chiba M, Hong S, Ojima T, Ueno Y, Bondoc E, Kobayashi K, Ishii M, Shimosegawa
        T. Analysis of the entire nucleotide sequence of hepatitis B virus genotype B in the Philippines reveals a new
        subgenotype of genotype B. J Gen Virol 2006; 87: 1175-1180   PubMed

92    Sakamoto T, Tanaka Y, Orito E, Co J, Clavio J, Sugauchi F, Ito K, Ozasa A, Quino A, Ueda R, Sollano J, Mizokami M.
        Novel subtypes (subgenotypes) of hepatitis B virus genotypes B and C among chronic liver disease patients in the
        Philippines. J Gen Virol 2006; 87: 1873-1882   PubMed

93    Sugauchi F, Mizokami M, Orito E, Ohno T, Kato H, Suzuki S, Kimura Y, Ueda R, Butterworth LA, Cooksley WG. A novel
        variant genotype C of hepatitis B virus identified in isolates from Australian Aborigines: complete genome sequence and
        phylogenetic relatedness. J Gen Virol 2001; 82: 883-892   PubMed   

94    Cavinta L, Sun J, Zarnekow M, Barzaga N, Schaefer S. New hepatitis B virus subgenotype C5 from the Philippines.

95    Kato H, Fujiwara K, Gish RG, Sakugawa H, Yoshizawa H, Sugauchi F, Orito E, Ueda R, Tanaka Y, Kato T, Miyakawa Y,
        Mizokami M. Classifying genotype F of hepatitis B virus into F1 and F2 subtypes. World J Gastroenterol 2005; 11: 6295-
        6304   PubMed

96    Norder H, Arauz-Ruiz P, Blitz L, Pujol FH, Echevarria JM, Magnius LO. The T(1858) variant predisposing to the precore
        stop mutation correlates with one of two major genotype F hepatitis B virus clades.
J Gen Virol 2003; 84: 2083-2087


97    Devesa M, Rodriguez C, Leon G, Liprandi F, Pujol FH. Clade analysis and surface antigen polymorphism of hepatitis B
        virus American genotypes. J Med Virol 2004; 72: 377-384   PubMed

98    Huy TT, Ushijima H, Sata T, Abe K. Genomic characterization of HBV genotype F in Bolivia: genotype F subgenotypes
        correlate with geographic distribution and T(1858) variant. Arch Virol 2006;
151: 589-597   PubMed

99    Hannoun C, Norder H, Lindh M. An aberrant genotype revealed in recombinant hepatitis B virus strains from Vietnam. J
        Gen Virol 2000;
81: 2267-2272   PubMed   

100  Owiredu WK, Kramvis A, Kew MC. Hepatitis B virus DNA in serum of healthy black African adults positive for hepatitis B
        surface antibody alone: possible association with recombination between genotypes A and D. J Med Virol 2001;
64: 441-
        454   PubMed

101  Bollyky PL, Rambaut A, Harvey PH, Holmes EC. Recombination between sequences of hepatitis B virus from different
        genotypes. J Mol Evol 1996;
42: 97-102   PubMed

102  Morozov V, Pisareva M, Groudinin M. Homologous recombination between different genotypes of hepatitis B virus. Gene
        2000; 260: 55-65   PubMed

103  Suwannakarn K, Tangkijvanich P, Theamboonlers A, Abe K, Poovorawan Y. A novel recombinant of Hepatitis B virus
        genotypes G and C isolated from a Thai patient with hepatocellular carcinoma. J Gen Virol 2005;
86: 3027-3030

104   Kumar S, Tamura K, Nei M. MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence
        alignment. Brief Bioinform 2004;
5: 150-163


S- Editor  Liu Y    L- Editor  Lutze M    E- Editor  Ma WH





Reviews Add

Related Articles:
Anti-HBV hairpin ribozyme-mediated cleavage of target RNA in vitro
p73beta inhibits transcriptional activities of enhancer I and X promoter in hepatitis B virus more efficiently than p73alpha
Establishment of transgenic mouse harboring hepatitis B virus (adr subtype) genomes
A comparative study on serologic profiles of virus hepatitis B
Humoral and cellular immunogenecity of DNA vaccine based on hepatitis B core gene in rhesus monkeys