Published online Feb 14, 2018. doi: 10.3748/wjg.v24.i6.680
Peer-review started: September 28, 2017
First decision: October 18, 2017
Revised: December 25, 2017
Accepted: January 18, 2018
Article in press: January 18, 2018
Published online: February 14, 2018
To determine the variability/conservation of the domain of hepatitis B virus (HBV) preS1 region that interacts with sodium-taurocholate cotransporting polypeptide (hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism (S267F, NTCP variant) in a Spanish population.
Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection (CHB) (n = 41, 73% Caucasians), patients with resolved HBV infection (n = 100, 100% Caucasians) and an HBV-uninfected control group (n = 105, 100% Caucasians). Variability/conservation of the amino acid (aa) sequences of the NTCP-interacting domain, (aa 2-48 in viral genotype D) and a highly conserved preS1 domain associated with virion morphogenesis (aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis.
The HBV preS1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21 (in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCP-interacting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies (25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms (34% vs 27.3%), according to consensus sequences from GenBank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable (limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant.
In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null.
Core tip: Simultaneous analysis of both viral and host features important for hepatitis B virus (HBV) entry into hepatocytes provided locally relevant preliminary information in a population previously uncharacterized in this regard. In-house developed next-generation sequencing was successfully used to investigate the variability of the preS1 region of the HBV large envelope protein, and real-time PCR melting curve analysis to detect the rs2296651 polymorphism (NTCP variant, S267F) in the HBV cellular receptor, NTCP. Results in a limited sample indicate that the features analyzed would not decrease the effectiveness of new therapies to block NTCP and avert HBV binding to hepatocytes in our particular CHB population.