Evolutionary analysis of HBV “S” antigen genetic diversity in Iranian blood donors: A nationwide study

Abstract

The genetic diversity of the HBV S gene has a significant impact on the prophylaxis and treatment of hepatitis B infection. The effect of selective pressure on this genetic alteration has not yet been studied in Iranian blood donors. To explore HBV evolution and to analyze the effects and patterns of hepatitis B surface antigen (HBsAg) mutations on blood screening assays, 358 Iranian blood donors diagnosed as asymptomatic HBV carriers were enrolled in this nationwide study. Large S and partial S genes were amplified and sequenced. HBV (sub) genotypes and synonymous and nonsynonymous mutations were investigated. The impact of naturally occurring mutations on HBsAg ELISA results was explored. Phylogenetic analyses revealed that isolated strains were of genotype D. The dominant subgenotype/subtype was D1/ayw2. Deletions and naturally occurring stop codons in the pre-S1 and major hydrophilic region (MHR) were identified. In total, 32.8% of the studied strains harbored 195 single or multiple mutations in the MHR, the majority of which were located at the first loop of the "a determinant" domain. The ayw2 subtype showed a significant effect on the ELISA signal/cut-off value and carried fewer mutations in the MHR. Nonsynonymous/synonymous substitution value indicated that negative selection was the dominant evolutionary force in the HBV S gene. This nationwide study revealed that mutation frequency of HBsAg among Iranian blood donors was much higher than previous reports from the different local regions. These findings regarding the significant differences in reactivity of ELISA among different subtypes of HBV and its correlation with the number of mutations at the MHR will be valuable to public health authorities.

Molecular characterization of hepatitis B virus (HBV) strains circulating in the northern coast of the Persian Gulf and its comparison with worldwide distribution of HBV subgenotype D1

“…Subtype adw2 was similarly thought to be exclusively of genotype A but was also discovered in subgenotype D1 strains [Veazjalali et al, ; Yousif and Kramvis, ]. Even though none of the strains in this study were of subtype adw2 , this particular subtype has been identified together with subgenotype D1 in our most recent study among blood donor isolates in Iran [Pourkarim et al, ] as well as in other studies [Veazjalali et al, ; Garmiri et al, ]. In a previous study, due to a mutation detected at serine‐127, one untypable subtype strain was detected in genotype D1 strains isolated from HBV carriers living in central, northern, and western Iran [Mohebbi et al, ].…”

Genetic variation of hepatitis B surface antigen among acute and chronic hepatitis B virus infections in The Netherlands

“…Twenty percent of the acute strains harbored variation within the HBsAg, whereas more than half of the chronic strains (53%) harbored variation within the HBsAg. Other studies have shown similar percentages, ranging from 40% to 55% variation, which were mostly among chronic GtD strains . The low diversity among GtA acute strains suggests that the transmission of GtA is sustained within the MSM community in The Netherlands and that there is little transmission from chronic cases leading to new infections.…”

Single-Molecule Sequencing Reveals Complex Genome Variation of Hepatitis B Virus during 15 Years of Chronic Infection following Liver Transplantation

“…An additional substitution of interest was the surface gene nonsynonymous mutation that resulted in S C69* (data not shown). This amino acid change was observed at T1 (89%) and T3 (97%) but at a much lower rate (13%) at T2 and would result in the production of a truncated S protein, which has been associated with false-negative HBsAg detection in diagnostic serological assays (40). The corresponding change in the overlapping P ORF was rtS78T (Fig.…”