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Two novel mutants of the hepatitis B virus surface antigen (HBsAg) were characterized. The mutants that were isolated from asymptomatic patients were found to be persistently positive for both HBsAg and anti-hepatitis B surface antibody (anti-HBs) and a long-lasting anti-HBc (core) IgM. Polymerase chain reaction (PCR) and sequencing were performed to surface antigen coding region and revealed two genotype D mutants HBV. Aligned with known HBsAg sequences from GenBank, the mutant variants matched to consensus with eight distinct genotypes (A to H) of hepatitis B virus. Multiple sequence alignment provided a more sensible way of detecting sequence homology and identifying the HBV isolates. From this alignment, certain positions were highly conserved with the previously identified recorded Egyptian isolates, while other positions were not. The importance of the two variants lies in the observation that mutations in the surface antigen coding region can change the immunodominant region structure and therefore alter the group specific determinant antigenicity. Phylogenetic tree based on HBsAg partial nucleotide sequence was displayed. In conclusion, by understanding the HBsAg major immunodominant region nucleotide sequence, highly sensitive diagnostic assays can be achieved for detection of HBV in clinical specimens. Control of these HBV mutants, which will require new drugs, vaccines, and treatment strategies, will become the next major challenge on the path to eventual elimination of HBV infection.

MOLECULAR GENETICS MUTATIONS OF THE S GENE OF HEPATITIS B HBV VIRUS IN EGYPTIAN PATIENTS