The Interferons – Characterization and Application

Anthony Meager is a Principal Scientist in the Division of Immunology and Endocrinology, The National Institute for Biological Standards and Control (NIBSC), UK. Following his PhD in Biochemistry (Warwick University, UK, 1972), he has carried out research in biochemistry, cell biology, immunology, virology, and cytokines, especially interferons (IFN) and tumor necrosis factor (TNF). He joined the NIBSC in 1980. Currently, he heads laboratories involved in the biological standardization of IFN and TNF, and research studies on the bioactivity and immunogenicity of cytokines. From 1990, he has also contributed to regulatory guidance on gene therapy, both for the European Medicines Agency and the World Health Organization.

Preface.List of Contributors.Color Plates.Section A: Molecular Aspects, Introduction and Purification.1 Type I Interferons: Genetics and Structure (Shamith A. Samarajiwa, William Wilson and Paul J. Hertzog).1.1 Introduction.1.2 The Type I IFN Genetic Locus.1.3 Type I IFN Genes.1.4 Type I IFN Gene-regulatory Regions.1.5 Evolution of the Type I IFNs.1.6 Natural and Induced Mutations in IFN Genes.1.7 Secondary Structural Features of Type I IFNs.1.8 The Structure of Type I IFNs.2 Activation of Interferon Gene Expression Through Toll-like Receptor-dependent and -independent Pathways (Peyman Nakhaei, Suzanne Paz and John Hiscott).2.1 Introduction.2.2 IFN-beta Gene Transcription.2.3 IRF Family Members.2.4 Role of IRFs in Virus-mediated IFN Activation.2.5 IFN Signaling Pathways.2.6 Conclusions.3 Interferon Proteins: Structure, Production and Purification (Dimitris Platis and Graham R. Foster).3.1 Introduction.3.2 The Structure of Type I IFNs.3.3 Production and Purification of Type I IFNs.3.4 Long-acting IFNs.3.5 Summary.4 Interferon-g: Gene and Protein Structure, Transcription Regulation, and Actions (Ana M. Gamero, Deborah L. Hodge, David M. Reynolds, Maria Cecilia Rodriguez-Galan, Mansour Mohamadzadeh and Howard A. Young).4.1 Introduction.4.2 IFN-gamma Gene Structure and Regulation.4.3 IFN--gamma Signal Transduction.4.4 IFN--gamma in Th Cell Development.4.5 IFN--gamma and DCs.4.6 IFN--gamma - Role in Tumor Development and Growth.4.7 Summary.5 Interferon and Related Receptors (Sidney Pestka and Christopher D. Krause).5.1 Introduction.5.2 IFNs and IFN-like Molecules in Brief.5.3 The Receptors.5.4 The Type I IFN Receptor.5.5 The Type II IFN (IFN-g) Receptor.5.6 The IL-28R1 and -10R2 Receptor Complex.5.7 Overview of Multichain Receptors.5.8 Global Summary.6 Type III Interferons: The Interferon-l Family (Sergei V. Kotenko and Raymond P. Donnelly).6.1 Introduction.6.2 The Class II Cytokine Receptor Family (CRF2) and their Ligands.6.3 Genomic Structure.6.4 Receptor Complex and Signaling.6.5 Biological Activities.6.6 The Murine IFN-l Antiviral System.6.7 Evolution of the IFN Family.6.8 Therapeutic Potential.6.9 Conclusions.Section B: Biological Properties.7 Biological Actions of Type I Interferons (Melissa M. Brierley, Jyothi Kumaran and Eleanor N. Fish).7.1 Introduction.7.2 Sources of Type I IFN Production and Secretion.7.3 Type I IFN Interactions with the Receptor Complex.7.4 Type I IFN-induced Signaling Cascades.7.5 IFN-inducible Biological Responses.7.6 Summary.8 Interferons and Apoptosis - Recent Developments (Michael J. Clemens and Ian W. Jeffrey).8.1 Introduction.8.2 The Role of IFN-regulated Genes in the Control of Apoptosis.8.3 The Protein Kinase PKR and the Phosphorylation of Polypeptide Chain Initiation Factor eIF2alpha.8.4 IFNs and the Apoptotic Effects of TRAIL.8.5 Signal Transduction Pathways for IFN-mediated Effects on Apoptosis.8.6 The Antiapoptotic Effects of IFNs.8.7 Conclusions.9 Viral Defense Mechanisms against Interferon (Santanu Bose and Amiya K. Banerjee).9.1 Introduction.9.2 Innate Immune Antiviral Defense Mechanisms of Host Cells.9.3 Evasion of IFN-mediated Antiviral Response.9.4 Concluding Remarks.Section C: Clinical Applications.10 Overview of Clinical Applications of Type I Interferons (Frank Muller).10.1 Introduction.10.2 Biological Effects.10.3 Type I IFN Products Currently Available or Under Development.10.4 Pharmacokinetics.10.5 Clinical Applications of Type I Interferons.10.6 IFN Toxicity.10.7 Type I IFNs in the Future.11 Clinical Applications of Interferon-gamma (Christine W. Czarniecki and Gerald Sonnenfeld).11.1 Introduction.11.2 IFN-gamma - The Molecule.11.3 FDA-approved Indications: Established Benefit and Risks.11.4 Infectious Diseases.11.5 Infection Following Serious Trauma.11.6 Atopic Dermatitis (AD).11.7 Idiopathic Pulmonary Fibrosis (IPF).11.8 Systemic Sclerosis (SSc).11.9 Radiation-induced Fibrosis.11.10 Chronic Hepatitis.11.11 Oncology Indications: Ovarian Cancer.11.12 Conclusions.Section D: Measurement of Interferons and Anti-Interferons.12 Measurement of Interferon Activities (Tony Meager).12.1 Introduction.12.2 The IFNs: Mechanisms of Action, Protein Induction and Biological Activities.12.3 Measurement of Biological Activities of IFNs.12.4 Regulatory Landscape.13 The Development and Measurement of Antibodies to Interferon (Sidney E. Grossberg and Yoshimi Kawade).13.1 Introductory Perspective.13.2 NAbs.13.3 Immunoassays for Non-NAbs.13.4 Epitope Analysis.13.5 Development of Antibodies during IFN Therapy.13.6 Summary.Index.