Interferons and Their Use in Persistent Viral Infections

Stephane Chevaliez and Jean-Michel Pawlotsky

Contents

1 Interferons 205

  1. 1 Type I IFNs 205
  2. 2 Type II IFNs 205
  3. 3 Type III IFNs 207

2 IFN Production during Viral Infections 207

  1. 1 Viral Triggering of IFN Production 207
  2. 2 IFN Gene Induction 209

3 Responses to IFN 210

  1. 1 IFN-InducedSignalingPathways 210
  2. 2 IFN Antiviral Effectors 211
  3. 3 Immunomodulatory Properties of IFNs 211

4 TherapeuticFormsofIFN 212

  1. 1 Standard IFN-« 212
  2. 2 Pegylated IFN-a 212
  3. 3 Other IFNs 213

5 IFN-BasedTreatment ofHepatitisCVirusInfection 214

  1. 1 Treatment of Chronic HCV Infection with IFN-a 214
  2. 2 Treatment of Acute HCV Infection with IFN-a 217
  3. 3 FuturePerspectivesofIFN-BasedHCVTherapy 217

6 IFN-Based Treatment of Hepatitis B Virus Infection 220

  1. 1 Treatment of Chronic HBV Infection with IFN-a 221
  2. 2 Treatment of Chronic HBV Infection with Other Type I IFNs 225
  3. 3 Treatment of Chronic HBV Infection with Type II IFN 226

7 IFN-Based Treatment of Hepatitis D/Delta Virus Infection 226

  1. 1 Standard IFN-a Monotherapy 226
  2. 2 Pegylated IFN-a Monotherapy 227
  3. 3 IFN-a Combination with Nucleoside/Nucleotide Analogues 227

8 Treatment of HIV Infection with IFN-a 228

  1. 1 Standard IFN-a 228
  2. 2 Pegylated IFN-a 229
  3. -M. Pawlotsky (k)

Department of Virology, HOpital Henri Mondor, 51 avenue du Marechal de Lattre de Tassigny,

94010 Creteil, France

[email protected]

H.-G. Krausslich, R. Bartenschlager (eds.), Antiviral Strategies, Handbook of Experimental 203 Pharmacology 189,

© Springer-Verlag Berlin Heidelberg 2009

9 Treatment of Other Viral Infections with Type IIFN

in Humans 229

10 Conclusion 230

References 230

Abstract In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN) by Isaacs and Lindenmann. Subsequently, the IFN-a gene was cloned, fully sequenced and IFN-a was produced in recombinant form. Recombinant IFN-a is now used as the basis for treatment of chronic hepatitis C virus infection and can also be used to treat certain forms of chronic hepatitis B virus infections. IFNs have also been used in other viral infections, although with less success. The antiviral mechanisms of IFNs are reviewed in this chapter as well as the utility of IFNs in the treatment of persistent viral infections.

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