Genogeography and Immune Epitope Characteristics of Hepatitis B Virus Genotype C Reveals Two Distinct Types: Asian and Papua-Pacific

Abstract

Distribution of hepatitis B virus (HBV) genotypes/subgenotypes is geographically and ethnologically specific. In the Indonesian archipelago, HBV genotype C (HBV/C) is prevalent with high genome variability, reflected by the presence of 13 of currently existing 16 subgenotypes. We investigated the association between HBV/C molecular characteristics with host ethnicity and geographical distribution by examining various subgenotypes of HBV/C isolates from the Asia and Pacific region, with further analysis on the immune epitope characteristics of the core and surface proteins. Phylogenetic tree was constructed based on complete HBV/C genome sequences from Asia and Pacific region, and genetic distance between isolates was also examined. HBV/C surface and core immune epitopes were analyzed and grouped by comparing the amino acid residue characteristics and geographical origins. Based on phylogenetic tree and geographical origins of isolates, two major groups of HBV/C isolates—East-Southeast Asia and Papua-Pacific—were identified. Analysis of core and surface immune epitopes supported these findings with several amino acid substitutions distinguishing the East-Southeast Asia isolates from the Papua-Pacific isolates. A west-to-east gradient of HBsAg subtype distribution was observed with adrq+ prominent in the East and Southeast Asia and adrq- in the Pacific, with several adrq-indeterminate subtypes observed in Papua and Papua New Guinea (PNG). This study indicates that HBV/C isolates can be classified into two types, the Asian and the Papua-Pacific, based on the virus genome diversity, immune epitope characteristics, and geographical distribution, with Papua and PNG as the molecular evolutionary admixture region in the switching from adrq+ to adrq-.

High Prevalence of Hepatitis B Virus Infection in Young Adults in Ternate, Eastern Indonesia

“…Nested polymerase chain reaction (PCR) using two sets of primers (S2-1/S1-2 [5′-CAA GGT ATG TTG CCC GTT TG-3′/5′-CGA ACC ACT GAA CAA ATG GC-3′] and S088/S2-2 [5′-TGT TGC CCG TTT GTC CTC TA-3′/5′-GGC ACT AGT AAA CTG AGC CA-3′]) was performed targeting an S gene segment encoding the "a" determinant of HBsAg. [30][31][32][33][34] Denaturation, annealing, and extension were done at 94°C for 30 seconds, 55°C for 30 seconds, and 72°C for 90 seconds/1 minute for the first/second PCR rounds (35/ 30 cycles), respectively. This nested PCR method was capable of detecting HBV DNA at very low titer (< 6 IU/mL), as validated using a panel of sera with known HBV DNA titers based on quantitative real-time PCR (Cobas TaqMan™ HBV Test; Roche Diagnostics, Indianapolis, IN) (Supplemental Table 1).…”

Hepatitis B virus and its sexually transmitted infection – an update

“…Based on some of the antigenic determinants of HBsAg, nine serological types - referred to as subtypes adw2 , adw4 , adrq+ , adrq , ayw1 , ayw2 , ayw3 , ayw4 and ayr - have been identified 50 . Ten genotypes of HBV (A-J) have been identified, and these correspond to specific geographic distributions 51 .…”

Hepatitis B virus pre-S2 deletion (nucleotide 1 to 54) in plasma predicts recurrence of hepatocellular carcinoma after curative surgical resection

“…Furthermore, we provided evidence supporting that patients with the pre-S2 deletion (nt 1 to 54) represented a population at high risk of HCC recurrence after curative surgical resection. Considering that the pre-S2 region (nt 1 to 54) coincides with the B-and T-cell epitopes of HBV large surface proteins [28,[38][39][40], the pre-S2 mutant proteins harboring the pre-S2 deletion (nt 1 to 54) may emerge as an immune escape mutant that may possibly explain their high incidence in HCC and high association with HCC recurrence after curative surgical resection.…”