Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population
Casillas, Rosario (Hospital Universitari Vall d'Hebron)
Tabernero, David (Hospital Universitari Vall d'Hebron)
Gregori i Font, Josep (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Belmonte, Irene (Hospital Universitari Vall d'Hebron)
Cortese, Maria Francesca (Hospital Universitari Vall d'Hebron)
González, Carolina (Hospital Universitari Vall d'Hebron)
Riveiro Barciela, Mar
López, Rosa Maria (Hospital Universitari Vall d'Hebron)
Quer, Josep 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Esteban, Rafael (Esteban Mur)
Buti, Maria
Rodríguez Frías, Francisco (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI14/01416 Instituto de Salud Carlos III PI15/00856
Note:	Altres ajuts: Cofinanced by the European Regional Development Fund (ERDF); and the Gilead Fellowship Program, No. GLD14-00296.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Hepatitis B virus ; Hepatitis B virus preS1 region ; Sodium-taurocholate co-transporting polypeptide ; NTCP-interacting domain ; Virion morphogenesis domain ; SNP rs2296651 ; Next-generation sequencing ; Real-time PCR melting curves
Published in:	World Journal of Gastroenterology, Vol. 24 (february 2018) , p. 680-692, ISSN 2219-2840

DOI: 10.3748/wjg.v24.i6.680
PMID: 29456407

14 p, 1.3 MB

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