Inspecting the Ribozyme Region of Hepatitis Delta Virus Genotype 1 : Conservation and Variability
Pacín Ruiz, Beatriz (Hospital Universitari Vall d'Hebron)
Cortese, Maria Francesca (Hospital Universitari Vall d'Hebron)
Tabernero, David (Hospital Universitari Vall d'Hebron)
Sopena, Sara (Hospital Universitari Vall d'Hebron)
Gregori i Font, Josep (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García-García, Selene (Hospital Universitari Vall d'Hebron)
Casillas, Rosario (Hospital Universitari Vall d'Hebron)
Najarro-Centeno, Adrián (Hospital Universitari Vall d'Hebron)
Aldama, Unai (Hospital Universitari Vall d'Hebron)
Palom, Adriana (Hospital Universitari Vall d'Hebron)
Rando-Segura, Ariadna (Hospital Universitari Vall d'Hebron)
Galán, Anna (Hospital Universitari Vall d'Hebron)
Vila, Marta (Hospital Universitari Vall d'Hebron)
Riveiro Barciela, Mar (Hospital Universitari Vall d'Hebron)
Quer, Josep 1963- (Hospital Universitari Vall d'Hebron. Institut de Recerca)
González-Aseguinolaza, Gloria (Univerdad de Pamplona)
Buti, Maria (Hospital Universitari Vall d'Hebron)
Rodríguez Frías, Francisco (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Fecha:	2022
Resumen:	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.
Ayudas:	Ministerio de Economía, Industria y Competitividad RTI2018-101936-B-I00 Instituto de Salud Carlos III PI20/016
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Hepatitis delta virus ; Ribozyme ; Next-generation sequencing ; Quasispecies ; Conservation ; Variability ; Viral fitness ; Persistence ; Target ; Gene silencing
Publicado en:	Viruses, Vol. 14 (january 2022) , ISSN 1999-4915

DOI: 10.3390/v14020215
PMID: 35215809

13 p, 1.5 MB

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