Genetic mutations of precore region of hepatitis B virus in hepatitis B e antigen-negative patients with fulminant hepatitis B and translation of precore variants in vitro.

OBJECTIVE

To detect mutations in precore region of hepatitis B virus of HBeAg negative- patients with fulminant hepatitis and to determine the effect of T1862 mutants on synthesis of precursor of hepatitis B e antigen.

METHODS

The entire precore and core region were amplified from sera of nine HBeAg negative-patients with fulminant hepatitis B by polymerase chain reaction (PCR). PCR products were cloned into plasmid pUC18, and sequencing for analysis of precore mutations. Precore and core sequence of T1862 variant were also cloned into expression plasmid pGEMT for in vitro transcription and translation study on synthesis and procession of e antigen.

RESULTS

Three variants, A1896, A1899 and T1862, whose nucleotide mutation led to amino acids substitutions, were detected in patients with fulminant hepatitis. T1862 variant didn't effect the synthesis of precursor of e antigen. Also there was no variant detected in precore region of hepatitis B virus in two patients.

CONCLUSIONS

The causes for negative of e antigen in fulminant hepatitis patients may be partially explained by precore mutation of A1896 and T1862, and the latter variant may effect the process of precursor of e antigen, rather than the synthesis of precursor protein.