Contribution of insertions and deletions to the variability of hepatitis C virus populations.
Little is known about the potential effects of insertions and deletions (indels) on the evolutionary dynamics of hepatitis C virus (HCV). In fact, the consequences of indels on antiviral treatment response are a field of investigation completely unexplored. Here, an extensive sequencing project was undertaken by cloning and sequencing serum samples from 25 patients infected with HCV subtype 1a and 48 patients with subtype 1b. For 23 patients, samples obtained after treatment with alpha interferon plus ribavirin were also available. Two genome fragments containing the hypervariable regions in the envelope 2 glycoprotein and the PKR-BD domain in NS5A were sequenced, yielding almost 16 000 sequences. Our results show that insertions are quite rare, but they are often present in biologically relevant domains of the HCV genome. Moreover, their frequency distributions between different time samples reflect the quasispecies dynamics of HCV populations. Deletions seem to be subject to negative selection.
Torres-Puente
Manuela
M
Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Departamento de Genética, Universidad de Valencia, Spain.
Cuevas
José M
JM
Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Departamento de Genética, Universidad de Valencia, Spain.
Jiménez-Hernández
Nuria
N
Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Departamento de Genética, Universidad de Valencia, Spain.
Bracho
María A
MA
Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Departamento de Genética, Universidad de Valencia, Spain.
García-Robles
Inmaculada
I
Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Departamento de Genética, Universidad de Valencia, Spain.
Carnicer
Fernando
F
Unidad de Hepatología, Hospital General de Alicante, Spain.
Del Olmo
Juan
J
Servicio de Hepatologia, Hospital Clínico de Valencia, Spain.
Ortega
Enrique
E
Unidad de Enfermedades Infecciosas, Hospital General de Valencia, Spain.
Moya
Andrés
A
Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Departamento de Genética, Universidad de Valencia, Spain.
González-Candelas
Fernando
F
Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Departamento de Genética, Universidad de Valencia, Spain.
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D017353:Gene Deletion; D005814:Genes, Viral / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000145:classification / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D012254:Ribavirin / Q000627:therapeutic use; D016415:Sequence Alignment; D013030:Spain; D013045:Species Specificity; D014759:Viral Envelope Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C091015:glycoprotein E2, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase