Effect of antiviral treatment and host susceptibility on positive selection in hepatitis C virus (HCV).
We have conducted a large sequence study of the E1-E2 and NS5A regions of the HCV, subtypes 1a and b, both in patients previously treated with interferon, and untreated patients, who later responded, or not, to a combination therapy based on interferon plus ribavirin. We have examined the role played by the number of positively selected sites on disease progression and its relationship with several variables such as patients' age, sex and their risk of acquiring the disease. We have detected three groups of patients that respond or not to combination therapy: responders of intermediate age, older non-responders and young non-responders, they possess an increasing average number of positively selected sites in the E1-E2 region, respectively. We conclude that the host's genetic factors play an important role in whether the disease is contained or becomes chronic.
Jiménez-Hernández
Nuria
N
Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, Spain.
Sentandreu
Vicente
V
Castro
José A
JA
Torres-Puente
Manuela
M
Bracho
Alma
A
García-Robles
Inmaculada
I
Ortega
Enrique
E
Del Olmo
Juan
J
Carnicer
Fernando
F
González-Candelas
Fernando
F
Moya
Andrés
A
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D012254:Ribavirin / Q000627:therapeutic use*; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014759:Viral Envelope Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D007372:Interferons; D012367:RNA, Viral; D012254:Ribavirin; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C087035:E1 protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase