Characteristics of S gene mutation in patients with occult HBV infection

Objective To analyze characteristics of HBV S gene mutation in one patient with occult hepatitis B virus infection, who was positive for serum HBV DNA for long term, but negative for HBsAg in order to reveal the correlation between S gene mutation and development of OBI as well as the progression of the liver disease. Methods Four serum samples were collected at different time-points for the use of amplifying HBV S gene and performing cloning-sequencing. The representative S mutants were selected to construct recombinant vectors for phenotype analysis. Results Several S-gene mutational patterns were detected in the samples, including pre-S1 large fragment deletion, s126-127 "RPCMNCTI" insertion, sQ129N, s131-133 TSM→NST, and classical sG145R mutations. In sequential 4 samples, s131-133 TSM→NST mutation was detected in 0%, 26%, 59% and 74% of viral clones, respectively. The pre-S1 large fragment deletion was constantly found in the 4 serum samples, accounting for 26%, 17%, 15% and 21% of detected viral clones, respectively. Phenotypic analysis showed that sQ129N and s131-133 TSM → NST mutations reduced the affinity of the antibody to HBsAg and increased the secretion of virus particles. Compared with the wild-type strain, the replication capacity and surface antigen promoter Ⅱ (SPⅡ) activity of large fragment-deleted (nt 3046-3177 deletion) strain were decreased by 43.7% and 97.2%, respectively. In addition, sG145R-induced impairment to secretion capacity of viral particles was verified. Conclusions Clinical presentations of long-term OBI of this HBV-infected patient could be caused by multiple S-gene mutants. Some S-gene mutations influence viral phenotypic characteristics, which might closely be related to the progression of liver disease. DOI: 10.11855/j.issn.0577-7402.2015.03.0