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J Gen Virol 85 (2004), 811-820; DOI 10.1099/vir.0.79811-0

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© 2004 Society for General Microbiology

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

Fuminaka Sugauchi1,2, Hiromitsu Kumada3, Subrat A. Acharya4, Santosh Man Shrestha5, Maria Teresita A. Gamutan6, Mobin Khan7, Robert G. Gish8, Yasuhito Tanaka1, Takanobu Kato1, Etsuro Orito2, Ryuzo Ueda2, Yuzo Miyakawa9 and Masashi Mizokami1

1 Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
2 Departments of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
3 Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
4 Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
5 Liver Foundation Nepal, Nepal
6 SanJuan de Dios Hospital, The Philippines
7 Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
8 Hepatology and Gastroenterology, California Pacific Medical Center, San Francisco, USA
9 Miyakawa Memorial Research Foundation, Tokyo, Japan

Correspondence
Masashi Mizokami
mizokami{at}med.nagoya-cu.ac.jp

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 ({varepsilon}) 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.

The sequences reported in this article have been deposited in the DDBJ/EMBL/GenBank databases under accession numbers AB116076AB116094.




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