Sequence variations of hepatitis B virus promoter regions in persistently infected patients

The HBV in the sera of two chronic active hepatitis patients were analyzed for the promoter sequence heterogeneity. In most cases, the proportion of a ny particular clone in the total viral populations was less than 50%, showi ng high mutation rates. In contrast, promoter sequences of HBV from asympto matic carriers revealed only a few point mutations with no deletions. HBV i n chronic patient harbored variants with multiple mutations throughout prom oters including 1762 (A-to-T), 1764 (G-to-A) double mutation in C promoter and deletions near CCAAT site in S promoter. Unlike other three promoter re gions, C, pre-S1 and S, of HBV which revealed a high level of sequence hete rogeneity, the X promoter region (from nt 985 to 1430) showed little sequen ce heterogeneity within a patient. However, the predominant viral clones in two patients were quite different from each other. In addition to mutation s in promoter regions, a deletion mutation in the translation start codon w as also found in pre-S1 gene. The results in this report indicate that the mutation rates are not the same in all four promoters and that one of the s trategies for maintaining persistent infection could be through mutations i n viral promoters which then impair the balance of viral gene expressions.