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 (epsilon) 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.
Sugauchi
Fuminaka
F
Departments of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.|Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Kumada
Hiromitsu
H
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.
Acharya
Subrat A
SA
Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
Shrestha
Santosh Man
SM
Liver Foundation Nepal, Nepal.
Gamutan
Maria Teresita A
MTA
SanJuan de Dios Hospital, The Philippines.
Khan
Mobin
M
Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
Gish
Robert G
RG
Hepatology and Gastroenterology, California Pacific Medical Center, San Francisco, USA.
Tanaka
Yasuhito
Y
Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Kato
Takanobu
T
Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Orito
Etsuro
E
Departments of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Ueda
Ryuzo
R
Departments of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Miyakawa
Yuzo
Y
Miyakawa Memorial Research Foundation, Tokyo, Japan.
Mizokami
Masashi
M
Departments of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
D000349:Africa / Q000453:epidemiology; D001208:Asia / Q000453:epidemiology; D001483:Base Sequence; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology* / Q000821:virology*; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D012689:Sequence Homology, Nucleic Acid
D004279:DNA, Viral