Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A Sugauchi, Fuminaka and Kumada, Hiromitsu and Acharya, Subrat A. and Shrestha, Santosh Man and Gamutan, Maria Teresita A. and Khan, Mobin and Gish, Robert G. and Tanaka, Yasuhito and Kato, Takanobu and Orito, Etsuro and Ueda, Ryuzo and Miyakawa, Yuzo and Mizokami, Masashi,, 85, 811-820 (2004), doi = https://doi.org/10.1099/vir.0.79811-0, publicationName = Microbiology Society, issn = 0022-1317, abstract= 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., language=, type=