The "interferon sensitivity determining region" of hepatitis C virus is a stable sequence element

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• The interferon sensitivity determining region (ISDR) in hepatitis C virus (HCV) nonstructural protein 5A is implicated in treatment response.
• Chronic HCV infection involves long-term viral persistence and potential sequence evolution.

Purpose of the Study:

• To investigate variations in the HCV ISDR after 12-14 years of chronic infection.
• To determine the correlation between ISDR sequence and interferon treatment response in patients infected with the same HCV isolate.

Main Methods:

• Direct sequencing of HCV ISDR from 13 chronically infected patients.
• Analysis of viral sequences from patients with varying interferon sensitivities (complete responders, non-responders, partial responders).

Main Results:

• The HCV-AD78 isolate's ISDR was classified as an intermediate type.
• Low nucleotide substitution rates (2.2x10(-3)/site/year) were observed in the ISDR before treatment, with minimal amino acid changes.
• No selection for wild-type ISDR was detected during interferon therapy in partial responders.

Conclusions:

• No correlation was found between the ISDR sequence and interferon response in this homogeneous patient group.
• The ISDR appears to be a stable sequence element, potentially explaining divergent findings in different geographical regions.