Inspecting the Ribozyme Region of Hepatitis Delta Virus Genotype 1

The hepatitis delta virus (HDV) genome has an autocatalytic region called the ribozyme, which is essential for viral replication. The aim of this study was to use next-generation sequencing (NGS) to analyze the ribozyme quasispecies (QS) in order to study its evolution and identify highly conserved...

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Detalhes bibliográficos
Autores: Pacín Ruiz, Beatriz|||0000-0001-8718-6589, Cortese, Maria Francesca|||0000-0002-4318-532X, Tabernero, David|||0000-0002-1146-4084, Sopena, Sara|||0000-0002-3309-5486, Gregori i Font, Josep|||0000-0002-4253-8015, García-García, Selene|||0000-0001-7697-2058, Casillas, Rosario|||0000-0002-6758-6734, Najarro-Centeno, Adrián, Aldama, Unai, Palom, Adriana|||0000-0002-0130-1302, Rando-Segura, Ariadna|||0000-0003-4555-7286, Galán, Anna, Vila, Marta|||0000-0001-9303-5189, Riveiro Barciela, Mar|||0000-0001-9309-2052, Quer, Josep|||0000-0003-0014-084X, González-Aseguinolaza, Gloria|||0000-0002-1600-4562, Buti, Maria|||0000-0002-0732-3078, Rodríguez Frías, Francisco|||0000-0002-9128-7013
Tipo de documento: artigo
Data de publicação:2022
País:España
Recursos:Universitat Autònoma de Barcelona
Repositório:Dipòsit Digital de Documents de la UAB
Idioma:inglês
OAI Identifier:oai:ddd.uab.cat:256377
Acesso em linha:https://ddd.uab.cat/record/256377
https://dx.doi.org/urn:doi:10.3390/v14020215
Access Level:Acceso aberto
Palavra-chave:Hepatitis delta virus
Ribozyme
Next-generation sequencing
Quasispecies
Conservation
Variability
Viral fitness
Persistence
Target
Gene silencing
Descrição
Resumo:The hepatitis delta virus (HDV) genome has an autocatalytic region called the ribozyme, which is essential for viral replication. The aim of this study was to use next-generation sequencing (NGS) to analyze the ribozyme quasispecies (QS) in order to study its evolution and identify highly conserved regions potentially suitable for a gene-silencing strategy. HDV RNA was extracted from 2 longitudinal samples of chronic HDV patients and the ribozyme (nucleotide, nt 688-771) was analyzed using NGS. QS conservation, variability and genetic distance were analyzed. Mutations were identified by aligning sequences with their specific genotype consensus. The main relevant mutations were tested in vitro. The ribozyme was conserved overall, with a hyper-conserved region between nt 715-745. No difference in QS was observed over time. The most variable region was between nt 739-769. Thirteen mutations were observed, with three showing a higher frequency: T23C, T69C and C64 deletion. This last strongly reduced HDV replication by more than 1 log in vitro. HDV Ribozyme QS was generally highly conserved and was maintained during follow-up. The most conserved portion may be a valuable target for a gene-silencing strategy. The presence of the C64 deletion may strongly impair viral replication, as it is a potential mechanism of viral persistence.

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