Sophisticated viral quasispecies with a genotype-related pattern of mutations in the hepatitis B X gene of HBeAg-ve chronically infected patients
Cortese, Maria Francesca (Hospital Universitari Vall d'Hebron)
González, Carolina (Hospital Universitari Vall d'Hebron)
Gregori i Font, Josep (Roche Diagnostics (Sant Cugat))
Casillas, Rosario (Hospital Universitari Vall d'Hebron)
Carioti, Luca (University of Rome Tor Vergata)
Guerrero Murillo, Mercedes (Hospital Universitari Vall d'Hebron)
Riveiro Barciela, Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Godoy, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sopena, Sara (Hospital Universitari Vall d'Hebron)
Yll, Marçal (Hospital Universitari Vall d'Hebron)
Quer, Josep 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rando-Segura, Ariadna (Hospital Universitari Vall d'Hebron)
Lopez-Martinez, Rosa (Hospital Universitari Vall d'Hebron)
Pacín Ruiz, Beatriz (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García-García, Selene (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Esteban, Rafael (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Tabernero, David (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Buti, Maria (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodríguez Frías, Francisco (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	Patients with HBeAg-negative chronic infection (CI) have not been extensively studied because of low viremia. The HBx protein, encoded by HBX, has a key role in viral replication. Here, we analyzed the viral quasispecies at the 5' end of HBX in CI patients and compared it with that of patients in other clinical stages. Fifty-eight HBeAg-negative patients were included: 16 CI, 19 chronic hepatitis B, 16 hepatocellular carcinoma and 6 liver cirrhosis. Quasispecies complexity and conservation were determined in the region between nucleotides 1255 and 1611. Amino acid changes detected were tested in vitro. CI patients showed higher complexity in terms of mutation frequency and nucleotide diversity and higher quasispecies conservation (p < 0. 05). A genotype D-specific pattern of mutations (A12S/P33S/P46S/T36D-G) was identified in CI (median frequency, 81. 7%), which determined a reduction in HBV DNA release of up to 1. 5 log in vitro. CI patients showed a more complex and conserved viral quasispecies than the other groups. The genotype-specific pattern of mutations could partially explain the low viremia observed in these patients.
Ajuts:	Instituto de Salud Carlos III PI18/01436
Drets:	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, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Infectious diseases ; Haplotypes ; Mutation ; Sequencing
Publicat a:	Scientific reports, Vol. 11 (february 2021) , ISSN 2045-2322

DOI: 10.1038/s41598-021-83762-4
PMID: 33603102

11 p, 1.1 MB

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