Subgenotypes of hepatitis B virus genotype D (D1, D2, D3 and D5) in India: differential pattern of mutations, liver injury and occult HBV infection.
Hepatitis B genotype D (HBV/D) is the most widespread genotype and exists as at least five subgenotypes (HBV/D1-D5). However, little is known about the association of virological characteristics with clinical differences among HBV/D subgenotypes. To investigate the virological characteristics of these subgenotypes and their clinical implications, we selected a cohort of 109 genotype D infected individuals from the state of West Bengal, India, including 68 HBsAg positive patients and 41 with occult HBV infection. Among the HBsAg positive subjects 28 had chronic hepatitis B virus infection, 40 were asymptomatic carriers based on clinical examination, liver function test and ultrasonograph results. Overall, HBV/D1 was found in 17%, HBV/D2 in 29%, HBV/D3 in 34% and HBV/D5 in 20% of the cases. HBV/D1 was significantly associated with chronic liver disease (P = 0.01), and in this subgenotype A1896 (PreC mutations) were most common. Although BCP mutations (A/C1753 and T1762/A1764) were found to be frequently associated with HBV/D2 (33% and 33%) and D5 (47% and 59%), no apparent clinical correlation was observed. On the other hand, occult HBV infection was significantly associated with HBV/D3 infection, along with low level of BCP and PreC mutations and several non-synonymous substitutions in the catalytic reverse transcriptase (RT) domain of polymerase gene. Similar nucleotide substitutions in the surface (S) gene region were observed from both northern and eastern Indian HBV/D3 isolates. In conclusion, HBV/D subgenotypes differ in their mutational patterns in the S, polymerase and the BCP/PreC regions that may influence their clinical outcomes.
Chandra
P K
PK
ICMR Virus Unit, Kolkata, India.
Biswas
A
A
Datta
S
S
Banerjee
A
A
Panigrahi
R
R
Chakrabarti
S
S
De
B K
BK
Chakravarty
R
R
D000293:Adolescent; D000328:Adult; D002648:Child; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D006515:Hepatitis B virus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D055815:Young Adult
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens