Evidence of an Exponential Decay Pattern of the Hepatitis Delta Virus Evolution Rate and Fluctuations in Quasispecies Complexity in Long-Term Studies of Chronic Delta Infection

Chronic HDV infection can cause a severe form of viral hepatitis for which there is no specific treatment. Characterization of the hepatitis B or C viral quasispecies has provided insight into treatment failure and disease recurrence following liver transplantation, has proven useful to understand h...

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Bibliographic Details
Published in:PloS one 2016-06, Vol.11 (6), p.e0158557-e0158557
Main Authors: Homs, Maria, Rodriguez-Frias, Francisco, Gregori, Josep, Ruiz, Alicia, Reimundo, Pilar, Casillas, Rosario, Tabernero, David, Godoy, Cristina, Barakat, Salma, Quer, Josep, Riveiro-Barciela, Mar, Roggendorf, Michael, Esteban, Rafael, Buti, Maria
Format: Article
Language:English
Subjects:
Adenosine
Analysis
Antigens
Biochemistry
Biological Evolution
Biology and Life Sciences
Chronic infection
Codons
Complexity
Correlation analysis
Decay rate
Evolution
Fluctuations
Gastroenterology
Genome, Viral
Genomes
Genomics
Health aspects
Hepatitis
Hepatitis B
Hepatitis B e antigen
Hepatitis B virus
Hepatitis C
Hepatitis C virus
Hepatitis D virus
Hepatitis D, Chronic - virology
Hepatitis delta virus
Hepatitis Delta Virus - genetics
Humans
Infection
Infections
Liver
Liver diseases
Liver transplantation
Longitudinal studies
Medical research
Medical treatment
Medicine and Health Sciences
Mutation
Pathology
Patients
Population studies
Prognosis
Recurrence (Disease)
Research and Analysis Methods
Ribonucleic acid
RNA
RNA Editing
RNA polymerase
RNA, Viral - genetics
Seroconversion
Stop codon
Substrates
Transplantation
Virus Replication
Viruses
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Summary:Chronic HDV infection can cause a severe form of viral hepatitis for which there is no specific treatment. Characterization of the hepatitis B or C viral quasispecies has provided insight into treatment failure and disease recurrence following liver transplantation, has proven useful to understand hepatitis B e antigen seroconversion, and has helped to predict whether hepatitis C infection will resolve or become chronic. It is likely that characterization of the hepatitis delta virus (HDV) quasispecies will ultimately have similar value for the management of this infection. This study sought to determine the RNA evolution rates in serum of chronic hepatitis delta (CHD) treatment-naïve patients, using next-generation sequencing methods. The region selected for study encompassed nucleotide positions 910 to 1270 of the genome and included the amber/W codon. Amber/W is a substrate of the editing process by the ADAR1 host enzyme and is essential for encoding the 2 delta antigens (HDAg). The amber codon encodes the small (unedited) HDAg form and the W codon the large (edited) HDAg form. The evolution rate was analyzed taking into account the time elapsed between samples, the percentage of unedited and edited genomes, and the complexity of the viral population. The longitudinal studies included 29 sequential samples from CHD patients followed up for a mean of 11.5 years. In total, 121,116 sequences were analyzed. The HDV evolution rate ranged from 9.5x10-3 to 1.2x10-3 substitutions/site/year and showed a negative correlation with the time elapsed between samples (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0158557