Genetic analysis ofprecore/coreand partialpolgenes in an unprecedented outbreak of fulminant hepatitis B in India

Abstract

SUMMARYWe investigated an unprecedented outbreak of fulminant hepatitis B virus (HBV) that occurred in Modasa, Gujarat (India) in 2009. Genomic analysis of all fulminant hepatic failure cases confirmed exclusive predominance of subgenotype D1. A1762T, G1764A basal core promoter (BCP) mutations, insertion of isoleucine after nt 1843, stop codon mutation G1896A, G1862T transversion plus seven other mutations in the core gene caused inhibition of HBeAg expression implicating them as circulatingprecore/BCP mutant virus. Two rare mutations at amino acids 89 (Ile→Ala) and 119 (Leu→Ser) in addition to other mutations in thepolymerase (pol)gene may have caused some alteration in either of fourpolgene domains to affect encapsidation of pregenomic RNA to enhance pathogenicity. Sequence similarity among patients' sequences suggested an involvement of a single hepatitis B mutant strain/source to corroborate the finding of gross and continued usage of HBV mutant-contaminated syringes/needles by a physician which resulted in this unprecedented outbreak of fulminant hepatitis B. The fulminant exacerbation of the disease might be attributed to mutations in the BCP/precore/coreandpolgenes that may have occurred due to selection pressure during rapid spread/mutation of the virus.