Adaptive evolution in the S gene of hepatitis B virus from patients with occult HBV infection / 中华微生物学和免疫学杂志

ABSTRACT

Objective To detect the positively selected sites in the surface ( S) gene of hepatitis B viruses ( HBVs) from patients with occult HBV infection and to study the molecular mechanism of occult HBV infection.Methods The sequence of S gene from patients with occult HBV infection and reference strains of eight HBV genotypes ( A through H) were downloaded from GenBank and then alignment analysis were performed by using Clustal W software .Phylogenetic trees were constructed by using MEGA 5.05 soft-ware package.PAML4.7 was used to analyze positively selected sites .Results A total of 1286 HBV se-quences from patients with occult infection were searched in GenBank .One hundred and seventy-four com-plete gene sequences encoding surface S protein were screened after alignment analysis and confirmation , of which 13 sequences with nonsense mutation were removed .The likelihood ratio test showed that for both the 161 remained sequences and the 31 reference sequences , the selection models of M2, M3 and M8 were sig-nificantly better than the neutral models of M0, M1 and M7 (2△lnL<55.12, P<0.001).By using Bayes Empirical Bayes (BEB) analysis, 14 positively selected sites (including codon 3, 8, 40, 45, 46, 47, 49, 68, 126, 127, 164, 184, 207 and 210) were detected in the surface gene of HBVs from patients with occult HBV infection, eight of which were located at the immune epitope of HBsAg .However, only 2 positively se-lected sites were identified in reference sequences .Conclusion The long-lasting persistence of HBV in pa-tients with occult HBV infection might be caused by the adaptive evolution of their surface gene in a form of escape mutant under immune suppressive condition .