Hepatitis B Virus Variants with Multiple Insertions and/or Deletions in the X Open Reading Frame 3' End

Deletions in the 3' end region of the hepatitis B virus (HBV) X open reading frame (HBX) may affect the core promoter (Cp) and have been frequently associated with hepatocellular carcinoma (HCC). The aim of this study was to investigate the presence of variants with deletions and/or insertions...

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Detalles Bibliográficos
Autores: García-García, Selene|||0000-0001-7697-2058, Caballero, Andrea|||0000-0003-2891-6347, Tabernero, David|||0000-0002-1146-4084, Cortese, Maria Francesca|||0000-0002-4318-532X, Gregori i Font, Josep|||0000-0002-4253-8015, Rodriguez-Algarra, Francisco|||0000-0002-4134-2141, Quer, Josep|||0000-0003-0014-084X, Riveiro Barciela, Mar|||0000-0001-9309-2052, Homs, Maria|||0000-0002-8370-8375, Rando-Segura, Ariadna|||0000-0003-4555-7286, Pacín Ruiz, Beatriz|||0000-0001-8718-6589, Vila, Marta|||0000-0001-9303-5189, Ferrer Costa, Roser|||0000-0002-8925-3172, Pumarola Suñé, Tomàs|||0000-0002-5171-7461, Buti, Maria|||0000-0002-0732-3078, Rodríguez Frías, Francisco|||0000-0002-9128-7013
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:259836
Acceso en línea:https://ddd.uab.cat/record/259836
https://dx.doi.org/urn:doi:10.3390/biomedicines10051194
Access Level:acceso abierto
Palabra clave:Hepatitis B virus
Hepatitis B X open reading frame
HBX 3' end region
Insertions
Deletions
Quasispecies
Next-generation sequencing
Descripción
Sumario:Deletions in the 3' end region of the hepatitis B virus (HBV) X open reading frame (HBX) may affect the core promoter (Cp) and have been frequently associated with hepatocellular carcinoma (HCC). The aim of this study was to investigate the presence of variants with deletions and/or insertions (Indels) in this region in the quasispecies of 50 chronic hepatitis B (CHB) patients without HCC. We identified 103 different Indels in 47 (94%) patients, in a median of 3.4% of their reads (IQR, 1.3-8.4%), and 25% (IQR, 13.1-40.7%) of unique sequences identified in each quasispecies (haplotypes). Of those Indels, 101 (98.1%) caused 44 different altered stop codons, the most commonly observed were at positions 128, 129, 135, and 362 (putative position). Moreover, 39 (37.9%) Indels altered the TATA-like box (TA) sequences of Cp; the most commonly observed caused TA2 + TA3 fusion, creating a new putative canonical TATA box. Four (8%) patients developed negative clinical outcomes after a median follow-up of 9.4 (8.7-12) years. In conclusion, we observed variants with Indels in the HBX 3' end in the vast majority of our CHB patients, some of them encoding alternative versions of HBx with potential functional roles, and/or alterations in the regulation of transcription.

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