Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A

Complete nucleotide sequences of 19 hepatitis B virus (HBV) isolates of genotype A (HBV/A) were determined and analysed along with those of 20 previously reported HBV/A isolates. Of the 19 HBV/A isolates, six including three from Japan and three from the USA clustered with the 14 HBV/A isolates from Western countries. The remaining 13 isolates including four from The Philippines, two from India, three from Nepal and four from Bangladesh clustered with the six HBV/A isolates reported from The Philippines, South Africa and Malawi. Due to distinct epidemiological distributions, genotype A in the 20 HBV isolates was classified into subtype Ae (e for Europe), and that in the other 19 into subtype Aa (a for Asia and Africa) provisionally. The 19 HBV/Aa isolates had a sequence variation significantly greater than that of the 20 HBV/Ae isolates (2·5±0·3 % vs 1·1±0·6 %, P<0·0001); they differed by 5·0±0·4 % (4·1–6·4 %). The double mutation (T1762/A1764) in the core promoter was significantly more frequent in HBV/Aa isolates than in HBV/Ae isolates (11/19 or 58 % vs 5/20 or 25 %, P<0·01). In the pregenome encapsidation (ε) signal, a point mutation from G to A or T at nt 1862 was detected in 16 of the 19 (84 %) HBV/Aa isolates but not in any of the 20 HBV/Ae isolates, which may affect virus replication and translation of hepatitis B e antigen. Subtypes Aa and Ae of genotype A deserve evaluation for any clinical differences between them, with a special reference to hepatocellular carcinoma prevalent in Africa.

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Molecular characteristics of hepatitis B virus genotype a confer a higher response rate to interferon treatment

Journal of Hepatology ◽

10.1016/s0168-8278(01)80922-3 ◽

2001 ◽

Vol 34 ◽

pp. 15-16 ◽

Cited By ~ 14

Author(s):

J. Hou ◽

R. Schilling ◽

H.L.A. Janssen ◽

R.A. Heijtink ◽

R. Williams ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Response Rate ◽

Molecular Characteristics ◽

Interferon Treatment ◽

Virus Genotype ◽

B Virus ◽

Genotype A

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Virological and clinical implication of core promoter C1752/V1753 and T1764/G1766 mutations in hepatitis B virus genotype D infection in Mongolia

Journal of Gastroenterology and Hepatology ◽

10.1111/j.1440-1746.2008.05321.x ◽

2008 ◽

Vol 23 (3) ◽

pp. 474-481 ◽

Cited By ~ 26

Author(s):

Abeer Elkady ◽

Yasuhito Tanaka ◽

Fuat Kurbanov ◽

Tsendsuren Oynsuren ◽

Masashi Mizokami

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Clinical Implication ◽

Core Promoter ◽

Virus Genotype ◽

B Virus

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Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C

Journal of Medical Virology ◽

10.1002/jmv.20504 ◽

2005 ◽

Vol 78 (1) ◽

pp. 60-67 ◽

Cited By ~ 13

Author(s):

Mariko Kobayashi ◽

Norio Akuta ◽

Fumitaka Suzuki ◽

Yoshiyuki Suzuki ◽

Yasuji Arase ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Virus Genotype ◽

B Virus ◽

Virological Outcomes ◽

Genotype A

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Novel Hepatitis B Virus Genotype A Subtyping Assay That Distinguishes Subtype Aa from Ae and Its Application in Epidemiological Studies

Journal of Virology ◽

10.1128/jvi.78.14.7575-7581.2004 ◽

2004 ◽

Vol 78 (14) ◽

pp. 7575-7581 ◽

Cited By ~ 15

Author(s):

Izumi Hasegawa ◽

Yasuhito Tanaka ◽

Anna Kramvis ◽

Takanobu Kato ◽

Fuminaka Sugauchi ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Clinical Manifestations ◽

The United States ◽

Sub Saharan Africa ◽

Virus Genotype ◽

Hbv Genotype ◽

Specificity And Sensitivity ◽

B Virus ◽

Genotype A

ABSTRACT The eight genotypes of hepatitis B virus (HBV) have different geographical distributions, virological characteristics, and clinical manifestations. A unique subtype of HBV genotype A (HBV/A) was reported in sub-Saharan Africa, raising the possibility that patients infected with this subtype (HBV/Aa [“a” for African and Asian]) may have different clinical outcomes than other HBV/A isolates (HBV/Ae [“e” for European]). Comparison between 30 HBV/Aa and 30 HBV/Ae isolates indicated that almost all HBV/Ae isolates had G at nucleotide (nt) 1809 and C at nt 1812, whereas HBV/Aa isolates had T1809/T1812. Taking advantage of these two single nucleotide polymorphisms (SNPs), a novel subtype-specific PCR assay in the X/precore/core region was developed. This assay was combined with a restriction fragment length polymorphism assay using BglII in a different region (nt 1984 to 1989), which has a SNP distinguishing HBV/Aa from HBV/Ae, resulting in 100% specificity for the combined assay. Application of the subtyping assay using sera from 109 paid donors in the United States indicated significantly different distributions of HBV/A subtypes among races; African-Americans, Caucasians, and Hispanics had HBV/Ae, whereas Asians had mainly HBV/Aa, suggesting that the HBV/Aa isolates may have been imported by recent immigration from Asia. In conclusion, the specificity and sensitivity of the combined subtyping assay were confirmed, and its usefulness was demonstrated in a practical context.

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Clinical features and prognosis of hepatocellular carcinoma with respect to pre-S deletion and basal core promoter mutations of hepatitis B virus Genotype C2

Journal of Medical Virology ◽

10.1002/jmv.22238 ◽

2011 ◽

Vol 83 (12) ◽

pp. 2088-2095 ◽

Cited By ~ 6

Author(s):

Han Jak Ryu ◽

Do Young Kim ◽

Jun Yong Park ◽

Hye Young Chang ◽

Myoung Ha Lee ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Clinical Features ◽

Core Promoter ◽

Basal Core Promoter ◽

Virus Genotype ◽

B Virus ◽

Promoter Mutations

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Regulation of Hepatitis B Virus Core Promoter by Transcription Factors HNF1 and HNF4 and the Viral X Protein

Journal of Virology ◽

10.1128/jvi.78.13.6908-6914.2004 ◽

2004 ◽

Vol 78 (13) ◽

pp. 6908-6914 ◽

Cited By ~ 60

Author(s):

Yanyan Zheng ◽

Jie Li ◽

Jing-hsiung Ou

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Binding Site ◽

Nuclear Receptors ◽

Double Mutant ◽

Core Promoter ◽

X Protein ◽

Double Mutation ◽

The Core ◽

B Virus

ABSTRACT Hepatitis B virus (HBV) core promoter contains a binding site for nuclear receptors. A natural double mutation in this binding site, which changes nucleotide (nt) 1765 from A to T and nt 1767 from G to A, selectively abolishes the binding of several nuclear receptors without affecting that of HNF4. This double mutation also creates a binding site for the transcription factor HNF1 and changes two amino acids in the overlapping X protein sequence. In this study, we have examined the roles of HNF1, HNF4, and the X protein in the regulation of the core promoter activities in Huh7 hepatoma cells. Our results indicate that HNF4 could stimulate the expression of the precore RNA and the core RNA from the core promoter of both the wild-type (WT) HBV and the double mutant, although its effect on the former was more prominent. In contrast, HNF1, which did not affect the WT core promoter, suppressed the precore RNA expression of the double mutant. Further analysis using HBV genomic constructs, with and without the ability to express the X protein, indicates that the X protein did not affect the HNF4 activity on the core promoter and affected the HNF1 activity on the core promoter of only the double mutant. Thus, our results indicate that the phenotypic differences of HBV WT and double-mutant core promoters are at least partially due to the differential activities of HNF1, HNF4, and the X protein on these two promoters.

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