Effect of antiviral treatment and host susceptibility on positive selection in hepatitis C virus (HCV)

• Published in: Virus research Vol. 131; no. 2; pp. 224 - 232
• Main Authors: Jiménez-Hernández, Nuria, Sentandreu, Vicente, Castro, José A., Torres-Puente, Manuela, Bracho, Alma, García-Robles, Inmaculada, Ortega, Enrique, del Olmo, Juan, Carnicer, Fernando, González-Candelas, Fernando, Moya, Andrés
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2008
• Subjects: Adult; Aged; Amino Acid Sequence; Amino Acid Substitution; Antiviral Agents - therapeutic use; E1–E2 region; Female; HCV; Hepacivirus - drug effects; Hepacivirus - genetics; Hepacivirus - isolation & purification; Hepatitis C - drug therapy; Hepatitis C - virology; Hepatitis C virus; Host genetic factors; Humans; Interferon treatment; Interferons - therapeutic use; Male; Middle Aged; Molecular Sequence Data; NS5A region; Positive selection; Response to combination therapy based on interferon plus ribavirin; Ribavirin - therapeutic use; RNA, Viral - genetics; Selection, Genetic; Sequence Analysis, DNA; Treatment Outcome; Viral Envelope Proteins - genetics; Viral Nonstructural Proteins - genetics; Host genetic factors; Response to combination therapy based on interferon plus ribavirin; Positive selection; NS5A region; Interferon treatment; HCV; E1–E2 region
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2007.09.012

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.