The Investigation of HBV Pre-S/S Gene Mutations in Occult HBV Infected Blood Donors with anti-HBs Positive

INTRODUCTION: The coexistence of hepatitis B virus (HBV) and hepatitis B surface antibodies (anti-HBs) in occult hepatitis B virus infection (OBI) is a contradictory phenomenon, and the underlying mechanism is not fully understood. The characteristics of pre-S/S mutations in OBI genotypes B and C (OBI(B) and OBI(C)) in the presence or absence of anti-HBs were analyzed extensively in this study. Methodology. The amino acid substitutions of envelope proteins of 21 OBI strains, including 4 HBs (+) OBI(B), 6 HBs (−) OBI(B), 6 HBs (+) OBIc, and 5 HBs (−) OBI(C) samples, were analyzed and fully compared among groups of HBV genotypes and the presence of anti-HBs. RESULTS: The mutation rates in pre-S1, pre-S2, and S proteins of OBI(C) were significantly higher than wild-type HBV (wt-HBV) genotype C strains, but only the mutation rate of S protein in OBI(B) was significantly higher compared to wild-type HBV genotype B. The mutation rates in S protein of anti-HBs (−) OBI were higher than anti-HBs(+) OBI samples (4.40% vs. 2.43% in genotype B, P > 0.05; 6.81% vs. 3.47% in genotype C, P < 0.05). For these high-frequency substitutions in the pre-S/S region, the mutations sN40S and sK122R were found in 27.3% and 45.5% of anti-HBs (−) OBI strains, respectively. 7 substitutions were uniquely found in OBI(C) strains and 9 substitutions were commonly detected in OBI(B) and OBI(C) strains. CONCLUSIONS: These results suggested that the mutations might occur randomly and were not selected by antibody pressure.