Book contents
- Frontmatter
- Contents
- Preface
- Foreword
- List of abbreviations
- Part I Basic principles
- 1 Background
- 2 The virus
- 3 Epidemiology and transmission
- 4 Natural history of infection
- 5 Pathogenesis of infection
- 6 Hepatitis C and hepatocellular carcinoma
- 7 Hepatitis C and autoimmune diseases
- 8 Clinical aspects of the disease
- 9 Current therapeutic approaches
- 10 Nonstructural protein 5A and interferon resistance
- Part II Recent advances
- Part III Experimental approaches
- Part IV Protocols and techniques
- Part V Some outstanding questions and emerging areas for investigation
- References
- Index
10 - Nonstructural protein 5A and interferon resistance
Published online by Cambridge University Press: 27 August 2009
- Frontmatter
- Contents
- Preface
- Foreword
- List of abbreviations
- Part I Basic principles
- 1 Background
- 2 The virus
- 3 Epidemiology and transmission
- 4 Natural history of infection
- 5 Pathogenesis of infection
- 6 Hepatitis C and hepatocellular carcinoma
- 7 Hepatitis C and autoimmune diseases
- 8 Clinical aspects of the disease
- 9 Current therapeutic approaches
- 10 Nonstructural protein 5A and interferon resistance
- Part II Recent advances
- Part III Experimental approaches
- Part IV Protocols and techniques
- Part V Some outstanding questions and emerging areas for investigation
- References
- Index
Summary
The observation that a poor IFN response in clinical trials correlated with a high degree of variability of quasispecies (Kanazawa et al., 1994; Chayama et al., 1995; Koizumi et al., 1995) (Ch. 9) implies that mutations in one or more HCV gene products may alter the sensitivity of the virus to IFN. Further work revealed the presence of an IFN sensitivity-determining region (ISDR) within the carboxy-terminal region of the NS5A polypeptide that spans amino acid residues 2209–2248 (Enomoto et al., 1995, 1996), which may be selected for during the course of IFN therapy (Enomoto et al., 1994). Patients that failed to respond to IFN therapy had one sequence within this region, while patients that were IFN responders had a ISDR sequence that differed in 4–11 amino acid residues. Among HCV sequences reported in the literature, the NS5A sequence associated with IFN resistance was identical to that of subtype 1b (Kato et al., 1990), implying that subtype 1b was associated with IFN resistance. The existence of an ISDR was confirmed by independent studies in Japan (Chayama et al., 1997; Kurosaki et al., 1997), but the correlation broke down when similarly designed studies were reported from other countries (Hofgartner et al., 1997; Squadrito et al., 1997).
- Type
- Chapter
- Information
- Hepatitis C VirusFrom Laboratory to Clinic, pp. 107 - 110Publisher: Cambridge University PressPrint publication year: 2002