Textbook of Influenza E-Book

Robert G. Webster

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 1405

Veröffentlichungsjahr: 2014

Beschreibung

The Textbook of Influenza is a comprehensive resource covering all aspects of influenza, from the genetic and molecular biology of the virus through to clinical aspects of the disease and the latest drug developments and treatments. This new edition has been completely revised and reflects the integration of disciplines concerning the emergence, evolution, pathogenesis and control of influenza viruses in the field of human and veterinary public health.

Textbook of Influenza examines the lessons learnt from the latest pandemic and provides the current state of knowledge for many yet unresolved issues related to virus origin, spread, pathogenesis and disease severity to better prepare for future pandemics. It covers the background to recent advances in influenza genomics and reverse genetics which have allowed the identification of virus virulence factors and the analysis and reconstruction of influenza viruses such as the 1918 Spanish flu strain.

This new edition is divided into eight key sections, containing chapters co-written by international experts from both the clinical and scientific communities, covering:
• Influenza Perspectives
• Structure and Replication
• Evolution and Ecology
• Epidemiology and Surveillance
• Immunology
• Vaccines and Vaccine Development
• Clinical Aspects and Antivirals
• Public Health

Textbook of Influenza is for all those working in the area of influenza including clinical and basic scientists, immunologists, molecular and structural virologists, public health officials and global pandemic control planners.

Leseprobe

Table of Contents

Title page

Copyright page

List of Contributors

Foreword to the Second Edition

Preface to the second edition

Acknowledgments

PART 1: Influenza: Perspective

1: Human influenza: One health, one world

Introduction

Global impact of influenza

Influenza in a crowded, connected, and converging world

Global interconnectedness requires global coordination and response

New opportunities in a changing world

Conclusions

Acknowledgments

2: Influenza pandemics: History and lessons learned

Introduction

Past and recent influenza pandemics

Lessons learned from past influenza pandemics

Conclusions

Acknowledgments

PART 2: Structure and replication

3: Structure, disassembly, assembly, and budding of influenza viruses

Introduction

Structure and virus morphology

Disassembly

Transport and assembly

Budding

Conclusions

Acknowledgments

4: The virus genome and its replication

The segmented RNA virus genome of influenza A and B viruses

Viral mRNA synthesis (transcription) and viral RNA replication

5: Influenza glycoproteins: Hemagglutinin and neuraminidase

HA and NA structures, functions, antigenicity and classification: An overview

Functions of hemagglutinin

Neuraminidase

Inhibitors of HA and NA functions and potential antiviral drugs

Antigenicity of HA and NA

6: Proton channels of influenza A and B viruses

Influenza A virus M2 protein

The A/M2 protein has ion channel activity that is required for efficient viral replication

M2 proton conduction mechanism

Atomic structures of the A/M2 channel

Inhibition of the A/M2 channel

New development of A/M2 channel inhibitors

Influenza B virus BM2 protein is also a proton channel

Note added in proof

Acknowledgments

7: The NS1 protein: A master regulator of host and viral functions

Introduction

General features and structures of the influenza A virus NS1 protein

Molecular and cellular functions

Unique function of the NS1 protein of influenza B virus (B/NS1): Binding IFN-induced ISG15

Regulation of the function of the NS1 protein of influenza A virus

Impact of the NS1 protein of influenza A virus in virulence, host tropism, and immune responses

NS1 protein as an antiviral target

NS1-modified viruses as potential live attenuated vaccines

Conclusions

8: Structure and function of the influenza virus replication machinery and PB1-F2

Architecture of the vRNP

Atomic structure of the influenza polymerase

Role of PB1-F2

Evolution and adaptation

Perspectives

Note added in proof

Acknowledgments

9: The genome and its manipulation: Recovery of the 1918 virus and vaccine virus generation

The pandemic 1918 virus – an elusive killer virus is identified

Virulence and pathogenicity of pandemic 1918 virus infections

Host responses to infection with pandemic 1918 virus

Bacterial coinfections in pandemic 1918 virus infections

Viral determinants of pandemic 1918 virus pathogenicity

Generation of vaccine viruses

10: Pathogenesis

Introduction

Disease in mammalian and avian hosts

Pathogenic mechanisms

Hemagglutinin determines tropism and spread of infection

Neuraminidase promotes virus release and destroys decoy receptors

Polymerase determines replication rates

NS1 modulates host responses

PB1-F2 and PA-X – other modulators of host responses

Acknowledgments

PART 3: Evolution and ecology of influenza viruses

11: Ecology and evolution of influenza viruses in wild and domestic birds

Introduction

Natural reservoirs

Influenza in domestic birds

Prevalence and perpetuation in poultry

HPAI H5N1 virus

Interspecies transmission

Evolution of influenza A virus in different hosts

Conclusions and outlook

12: Influenza in swine

Influenza as a swine disease

Molecular epidemiology of swine influenza viruses

Cross-species transmission of swine influenza viruses

Swine as intermediate hosts

Challenges to the control of swine influenza

Challenges in swine influenza surveillance

Knowledge gaps

Acknowledgments

13: Equine/Canine/Feline/Seal influenza

Equine influenza

Canine influenza

Feline influenza

Influenza in marine mammals

Acknowledgments

14: Emergence and evolution of the 1918, 1957, 1968, and 2009 pandemic virus strains

Definition of pandemic influenza disease

Background

Determinants of evolution and emergence of pandemic influenza virus strains

The 1918, 1957, 1968, and 2009 influenza virus pandemics

Future influenza pandemics

PART 4: Epidemiology and surveillance

15: Influenza surveillance and laboratory diagnosis

Surveillance

Laboratory diagnosis

Transport

Conclusions

16: Epidemiology of influenza

Introduction

Seasonal influenza surveillance, epidemiology, and burden

Interventions for seasonal influenza

Pandemic influenza

PART 5: Immunology of influenza

17: Innate immunity

Introduction

Innate sensors of influenza virus infection

Type I interferon-mediated antiviral defense mechanisms

ISG15

Cell types involved in innate defense against influenza virus

Dendritic cells – innate link to adaptive immunity

Innate immune responses and the pathogenesis of influenza

Conclusions

18: Antibody-mediated immunity

Antibody response to influenza virus

Induction of B-cell responses to influenza antigen

Viral targets of the antibody response to influenza virus

Antibody-mediated immune pressure selects for antigenic “drift” and “shift”

Role of pre-existing antibodies for the outcome after influenza infection

Function of antibodies in infection with and clearance from influenza virus

Conclusions

19: Cell-mediated immunity

Introduction

T-cell recognition of viral antigens

Primary T-cell response to influenza viruses

Mechanisms of T-cell-mediated viral control

T-cell memory to influenza viruses

Human immunity to influenza viruses

Implications of T-cell immunity for the design of influenza vaccines

Conclusions

Acknowledgments

PART 6: Vaccines and vaccine development

20: Immunogenicity, efficacy of inactivated/live virus seasonal and pandemic vaccines

Introduction

Inactivated influenza vaccine

Live influenza vaccines

Comparisons of inactivated and live influenza vaccines

21: New approaches to vaccination

Introduction

Structural basis for development of universal influenza vaccines

New approaches to elicit cross-protective immunity against influenza virus

Conclusions

22: Control of influenza in animals

Introduction

Birds

Mammals

Control strategies for influenza in mammals

Control strategies for influenza in birds

Direct control measures for poultry

Types of avian influenza vaccines

Use of avian influenza vaccines

Detection of infection in vaccinated flocks and vaccinated birds

Conclusions

Acknowledgment

23: Influenza vaccine production

Enormous progress in influenza vaccine manufacturing

Vaccine development differs from that of pharmaceutical products

Vaccine production is complex: Barriers to entry are exceptionally high

Vaccine production capacities unevenly distributed globally

Influenza vaccine production: Driven by disease seasonality and virus evolution

Prerequisites for vaccine production

Manufacturing of influenza vaccines

PART 7: Clinical aspects and antivirals

24: Human influenza: Pathogenesis, clinical features, and management

Introduction

Pathogenesis

Clinical manifestations

Diagnosis

Management considerations

25: Antivirals: Targets and use

Introduction

Mechanism of action and resistance

Approved agents

Investigational agents in clinical development

Investigational agents in preclinical development

Combination therapy

Efficacy and use

Recommendations for use by national and international organizations

Emergence of resistance

26: The control of influenza and cost-effectiveness of interventions

Introduction

Tools for the prevention and control of influenza

Combined approaches for the control of influenza outbreaks

Introduction to applied health economics

Key factors in the economics of influenza vaccination

Evidence of cost-effectiveness of vaccination

Evidence of cost-effectiveness of antiviral prophylaxis or treatment

Conclusions

Acknowledgments

27: Applications of quantitative modeling to influenza virus transmission dynamics, antigenic and genetic evolution, and molecular structure

Introduction

Transmission dynamic models

Antigenic analyses

Genetic and evolutionary models

Computational structural analyses

Conclusions

28: Pandemic preparedness and response

Historical context of health emergency planning and response

Preparedness and response to pandemics of the twentieth century

Modern day pandemic preparedness

Specific elements of pandemic preparedness

The 2009–2010 pandemic response

The future of pandemic preparedness

Acknowledgments

29: Influenza: The future

The next influenza pandemic

Genetic engineering, influenza, and dual-use research of concern

Public health: Harnessing the social network

New drug targets

Prospects for the “universal vaccine”

Is the end in sight?

PART 8: The outbreak of H7N9

30: Appendix

An outbreak of influenza H7N9 in China: Implications for influenza evolution and pandemic preparedness

The cases of human infection

Susceptibility to infection and pattern of disease

The virus

H7N9 and pandemic preparedness

An early perspective!

Index

This edition first published 2013 © 2013 by John Wiley & Sons, Ltd.

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Library of congress cataloging-in-publication data

Textbook of influenza / edited by Robert G. Webster, Arnold S. Monto, Thomas J. Braciale, Robert A. Lamb. – 2nd edition.

p. ; cm.

Includes bibliographical references and index.

ISBN 978-0-470-67048-4 (hardback : alk. paper) – ISBN 978-1-118-63681-7 – ISBN 978-1-118-63682-4 (eMobi) – ISBN 978-1-118-63683-1 (ePub) – ISBN 978-1-118-63684-8 (ePDF)

I. Webster, Robert G., 1932- editor of compilation. II. Monto, Arnold S., editor of compilation. III. Braciale, Thomas J., editor of compilation. IV. Lamb, Robert A., editor of compilation.

[DNLM: 1. Influenza, Human. WC 515]

RC150

616.2'03–dc23

2013010901

A catalogue record for this book is available from the British Library.

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover image: © Science Photo Library/Coloured TEM of a single influenza virus

Cover design by Meaden Creative

List of Contributors

Dennis J. Alexander, OBE, PhD, FSB, FRCPath, DSc

Formerly Head, Virology Department

Animal Health and Veterinary Laboratories

Weybridge, Addlestone, Surrey, UK

Rilwan A. Balogun

Microbiology, Immunology and Molecular Genetics

David Geffen School of Medicine

University of California, Los Angeles; and

California NanoSystems Institute (CNSI)

Los Angeles, CA, USA

Nicole Baumgarth, DVM, PhD

Professor, Center for Comparative Medicine and

Department of Pathology, Microbiology and

Immunology, University of California

Davis, CA, USA

Thomas J. Braciale, MD, PhD

Director, Beirne B. Carter Center for Immunology

Research, Beirne B. Carter Professor in Immunology

Professor of Pathology and Microbiology, Immunology, and Cancer Biology

University of Virginia School of Medicine

Charlottesville, VA, USA

Joseph Bresee, MD

Chief, Epidemiology and Prevention Branch

Influenza Division

Centers for Disease Control and Prevention

Atlanta, GA, USA

Carolyn B. Bridges, MD, FACP

CAPT USPHS, Associate Director for Adult

Immunizations, Immunization Services Division

National Center for Immunizations and Respiratory Diseases

Centers for Disease Control and Prevention

Atlanta, GA, USA

Ilaria Capua, DVM, PhD

Director, OIE/FAO Reference Laboratory for Avian

Influenza and Newcastle Disease

OIE Collaborating Center for Diseases

at the Human-Animal Interface

Istituto Zooprofilattico Sperimentale delle Venezie

Padua, Italy

Michael C. Carroll, PhD

Professor, Department of Pediatrics

Harvard Medical School; and

Program in Cellular and Molecular Medicine

Children's Hospital, Boston, MA, USA

Thomas M. Chambers, PhD

Professor, Gluck Equine Research Center

Department of Veterinary Science

University of Kentucky

Lexington, KY, USA

Nancy J. Cox, PhD

Director, Influenza Division

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Atlanta, GA, USA

Menno D. de Jong, MD, PhD

Professor in Clinical Virology

Head of Department of Medical Microbiology

Academic Medical Center

University of Amsterdam, Amsterdam

The Netherlands

Peter C. Doherty, PhD, FRS

Department of Microbiology and Immunology

The University of Melbourne, Melbourne, VIC, Australia; and

Department of Immunology

St Jude Children's Research Hospital

Memphis, TN, USA

Ruben O. Donis, DVM, PhD

Centers for Disease Control and Prevention

Atlanta, GA, USA

Edward J. Dubovi, PhD

Director, Virology Section

Animal Health Diagnostic Center

College of Veterinary Medicine

Cornell University

Ithaca, NY, USA

Damian C. Ekiert, PhD

Department of Integrative Structural and

Computational Biology

The Scripps Research Institute

La Jolla, CA, USA

Ervin Fodor, DPhil

Professor of Virology

Sir William Dunn School of Pathology

University of Oxford, Oxford, UK

Ron A. M. Fouchier, PhD

Professor in Molecular Virology

Department of Viroscience

Erasmus MC Rotterdam, The Netherlands

Steven J. Gamblin, PhD, FRS, FMedSci

MRC, National Institute for Medical Research

London, UK

Adolfo García-Sastre, PhD

Professor, Department of Microbiology

Fishberg Professor, Department of Medicine

Division of Infectious Diseases; and

Director Global Health and Emerging Pathogens Institute

Icahn School of Medicine at Mount Sinai

New York, NY, USA

Wolfgang Garten, PhD

Professor, Institut für Virologie

Philipps-Universität Marburg

Marburg, Germany

Santiago Gonzalez, PhD

Institute for Research in Biomedicine

Bellinzona, Switzerland

Yi Guan, PhD, MD

Director, State Key Laboratory of Emerging

Infectious Diseases

The University of Hong Kong; and

Professor, Centre of Influenza Research

and School of Public Health

Li Ka Shing Faculty of Medicine

The University of Hong Kong

Hong Kong SAR, China

Alan J. Hay, PhD

Virology Division, MRC National Institute

for Medical Research, London, UK

Frederick G. Hayden, MD

Professor of Medicine

Stuart S. Richardson Professor of Clinical Virology

University of Virginia School of Medicine

Charlottesville, VA, USA

Michael G. Ison, MD, MS, FIDSA

Associate Professor of Medicine and Surgery

Divisions of Infectious Diseases and Organ

Transplantation, Northwestern University

Feinberg School of Medicine

Chicago, IL, USA

Akiko Iwasaki, PhD

Professor, Department of Immunobiology

Howard Hughes Medical Institute

Yale University School of Medicine

New Haven, CT, USA

Daniel B. Jernigan, MD, MPH

Deputy Director, Influenza Division, National

Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention

Atlanta, GA, USA

Yoshihiro Kawaoka, DVM, PhD

Professor of Virology, Influenza Research Institute

Department of Pathobiological Sciences

School of Veterinary Medicine

University of Wisconsin-Madison, Madison WI, USA; and

Department of Special Pathogens

International Research Center for Infectious Diseases

Institute of Medical Science

University of Tokyo; and

Division of Virology

Department of Microbiology and Immunology

Institute of Medical Science

University of Tokyo; and

ERATO Infection-Induced Host Responses Project

Saitama, Japan

Wendy A. Keitel, MD

Kyle and Josephine Morrow Chair in Molecular

Virology and Microbiology; and

Professor, Molecular Virology and Microbiology

and Medicine, Baylor College of Medicine

Houston, TX, USA

Anne Kelso, PhD

Director, WHO Collaborating Centre for

Reference and Research on Influenza

North Melbourne, VIC, Australia

Hans-Dieter Klenk, MD

Professor Emeritus, Institut für Virologie

Philipps-Universität Marburg

Marburg, Germany

Robert M. Krug, PhD

Professor and Chair

Department of Molecular Genetics and Microbiology

Fellow, Mr. and Mrs. Corbin J. Robertson

Sr. Regents Chair in Molecular Biology

Institute for Cellular and Molecular Biology

University of Texas at Austin

Austin, TX, USA

Robert A. Lamb, PhD, ScD

John Evans Professor of Molecular and Cellular

Biology, Howard Hughes Medical Institute

Department of Molecular Biosciences

Northwestern University

Evanston, IL, USA

Gwendolyn Lee

Microbiology, Immunology and Molecular Genetics

David Geffen School of Medicine

University of California, Los Angeles; and

California NanoSystems Institute (CNSI)

Los Angeles, CA, USA

Marc Lipsitch, DPhil

Professor of Epidemiology

Center for Communicable Disease Dynamics

Harvard School of Public Health

Boston, MA, USA

Chunlong Ma, PhD

Research Associate, Department of Neurobiology

Department of Molecular Biosciences

Northwestern University, Evanston, IL, USA

Mikhail Matrosovich, PhD

Group Leader, Institut für Virologie

Philipps-Universität Marburg

Marburg, Germany

Jonathan A. McCullers, MD

Dunavant Professor and Chair

Department of Pediatrics

University of Tennessee Health Sciences Center; and

Pediatrician-in-Chief

Le Bonheur Children's Hospital, Memphis; and

Member, Department of Infectious Diseases

St. Jude Children's Research Hospital

Memphis, TN, USA

Andrew Mehle, PhD

Assistant Professor

Department of Medical Microbiology and Immunology

University of Wisconsin Madison

Madison, WI, USA

Martin I. Meltzer, MS, PhD

Senior Health Economist and

Distinguished Consultant

Lead, Health Economics and Modeling Unit (HEMU)

Division of Preparedness and Emerging Infections

National Center for Emerging and Zoonotic

Infectious Diseases

Centers for Disease Control and Prevention

Atlanta, GA, USA

Arnold S. Monto, MD

Thomas Francis, Jr. Collegiate Professor

of Epidemiology

School of Public Health

University of Michigan

Ann Arbor, MI, USA

Gary J. Nabel, MD, PhD

Senior Vice President, Chief Scientific Officer

Sanofi, Cambridge, MA, USA

Debiprosad Nayak, BVSc, PhD

Distinguished Professor Emeritus

Microbiology, Immunology and Molecular Genetics

David Geffen School of Medicine

University of California

Los Angeles, CA, USA

Gabriele Neumann, PhD

Research Professor, Influenza Research Institute

Department of Pathobiological Sciences

School of Veterinary Medicine

University of Wisconsin-Madison

Madison, WI, USA

Kathleen M. Neuzil, MD, MPH

Director, Vaccine Access and Delivery Global

Program, PATH, Clinical Professor

Departments of Medicine and Global Health

University of Washington

Seattle, WA, USA

Jonathan S. Nguyen-Van-Tam, MBE, BMedSci, BM BS, DM, FFPH, FRSPH, FSB

Professor of Health Protection

Health Protection and Influenza Research Group

University of Nottingham Medical School

City Hospital, Nottingham, UK

Peter Palese, PhD

Professor and Chair, Department of Microbiology

Department of Medicine

Mount Sinai School of Medicine

New York, NY, USA

Samuel K. Peasah, PhD, MBA

Health Economist

Epidemiology & Prevention Branch

Influenza Division/NCIRD/Centers for

Disease Control and Prevention

Atlanta, GA, USA

Malik Peiris, PhD, MD

Centre of Influenza Research and School of Public

Health, Li Ka Shing Faculty of Medicine

The University of Hong Kong

Hong Kong SAR, China

Lawrence H. Pinto, PhD

Professor Emeritus

Department of Neurobiology

Northwestern University

Evanston, IL, USA

Juergen A. Richt, DVM, PhD

Regents Distinguished Professor

Kansas State University

Manhattan, KS, USA

Rupert J. Russell

University of St Andrews, Fife, UK

[Deceased]

Sir John J. Skehel, PhD, FRS, FMedSci

MRC, National Institute for Medical Research

London, UK

Sakar Shivakoti, PhD

Microbiology, Immunology and Molecular Genetics

David Geffen School of Medicine

University of California, Los Angeles CA, USA; and

California NanoSystems Institute (CNSI)

Los Angeles, CA, USA

Derek Smith, BTech, MSc, MA, PhD

Professor of Infectious Disease Informatics

Center for Pathogen Evolution

WHO Collaborating Centre for Modeling Evolution

and Control of Emerging Infectious Diseases

Department of Zoology

University of Cambridge

Cambridge, UK

Klaus Stöhr, PhD, DVM

Vice-President, Head, Global Policy

Novartis Vaccines and Diagnostics, Inc

Cambridge, MA, USA

John Treanor, MD

Professor of Medicine, Microbiology and

Immunology, University of Rochester Medical Center

Rochester, NY, USA

Stephen J. Turner, PhD

Professor, Department of Microbiology and

Immunology, The University of Melbourne

Melbourne, VIC, Australia

Taia T. Wang, MD, PhD

Instructor in Clinical Investigation

Laboratory of Molecular Genetics and Immunology

Rockefeller University

New York, NY, USA

Richard Webby, PhD

Division of Virology

Department of Infectious Diseases

St. Jude Children's Research Hospital

Memphis, TN, USA

Robert G. Webster, PhD, FRS

Rose Marie Thomas Chair

Division of Virology

Department of Infectious Diseases

St Jude Children's Research Hospital

Memphis, TN, USA

Chih-Jen Wei, PhD

Associate Director for Research

Virology Laboratory and Vector Core Section

Vaccine Research Center

NIAID, National Institutes of Health

Bethesda, MD, USA

Marc-Alain Widdowson, VetMB, MA, MSc

Lead, International Epidemiology and Research

Team, Epidemiology and Response Branch

Influenza Division

Centers for Disease Control and Prevention

Atlanta, GA, USA

Ian A. Wilson, DSc, FRS

Professor, Department of Integrative Structural

and Computational Biology; and

IAVI Neutralizing Antibody Center and

Scripps Center for HIV/AIDS Vaccine Immunology

and Immunogen Discovery

The Scripps Research Institute

La Jolla, CA, USA

Maria Zambon, BSc, BM, BCh, PhD, FRCPath, FMedSci

Director of Reference Microbiology

Public Health England

London, UK

Z. Hong Zhou, PhD

Professor, Microbiology, Immunology

and Molecular Genetics

David Geffen School of Medicine

University of California, Los Angeles; and

California NanoSystems Institute (CNSI)

Los Angeles, CA, USA

Foreword to the Second Edition

In the Foreword to the First Edition of the Textbook of Influenza, David Tyrrell, one of the early expert researchers on influenza virus, wrote that although there were many original articles, review articles, and book chapters on both clinical and laboratory aspects of influenza, there was a need for a comprehensive book covering influenza from the bedside to basic molecular biology of virus to antiviral drug development. Such a book would enable investigators in the various fields of research to benefit from up-to-date knowledge in areas of research other than theirs. The First Edition was written to meet that need and I think that readers would agree that it indeed did so.

It is also clear, that in the years since that edition, there has been an extraordinary accumulation of knowledge on all aspects of influenza, and that progress is continuing at a rapid pace. Thus, the Second Edition is needed. A look at the titles and authors of the chapters of that edition attests to that. It is noteworthy that in addition to a large number of experts that contributed to the First Edition there are also new editors and new authors in the Second. This is in keeping with the fact that the topics are so important, new approaches and techniques have been developed, and the progress made so great. There is ample reason to believe that the Second Edition will meet the needs as well as, or better than, the First. In addition, it is very likely that, because of rapid advances, in several years a Third Edition will also be needed. It is also possible another reason will be that the virus still has some more surprises up its sleeve!

If one were to judge viruses on the basis of cleverness, it is fair to say that influenza virus would be among the most clever. If a virus's goals were to survive and infect the maximum number of hosts and individuals, to maintain large reservoirs in hosts with the ability to move between hosts, to evade immune responses, either natural, through previous exposure, or vaccination, influenza virus does all of the above very well. A short incubation period and replication in the respiratory tract also help. Compare it to its fellow RNA viruses, measles and yellow fever, which are still preventable by vaccines that have been available for many years. Also think about features of the structure and replication of the influenza virus. It is a great advantage for the virus to survive change and avoid immune responses if its genetic material is in not one but several pieces that can be exchanged within infected hosts, to have receptors widely available on host cells, and because the virus particle is assembled at the cell surface, to have an enzyme that can destroy the receptors and thus enable the virus to leave the cell surface and spread more easily. For all these reasons and more, the battle with influenza viruses will require continued research using a wide variety of current and new approaches and techniques and the publication of these results in volumes such as this Second Edition of the Textbook of Influenza.

I arrived at the Rockefeller Institute (soon to change its name to the Rockefeller University) in the summer of 1957 to begin a postdoctoral fellowship. This was a very fortunate time and place for me for several reasons. First, I joined the laboratory of Frank Horsfall and Igor Tamm, two very distinguished virologists and excellent mentors. In addition, also still active there were several other giants in virology. Peyton Rous, discoverer of the Rous sarcoma virus, the first virus to be shown to cause cancer, Richard Shope, who isolated both swine influenza virus, the first influenza virus to be isolated from a mammal, and the Shope papilloma virus, the first to be shown to cause a tumor in a mammal. Thomas Rivers, though not still active in the laboratory was very much around and editing. He was considered by many to be the Dean of Virology from the 1920s to the 1950s. In 1928 he edited the first comprehensive book on viruses, Filterable Viruses, and, in 1948, 1952, and 1959, three comprehensive and excellent editions of Viral and Rickettsial Diseases of Man; the third of these was co-edited by Frank Horsfall. A Fourth Edition was edited by Horsfall and Tamm. These volumes might be considered in a way as predecessors of the Textbook of Influenza.

The timing for me to arrive at the Rockefeller Institute in 1957 was very good because the Asian influenza pandemic had begun that spring in the Far East, and reached the United States that summer. It was caused by a virus that came to be known as H2N2. From September to November of 1957, I isolated six strains of influenza virus from patients at the Hospital of the Rockefeller Institute, the fifth of which I isolated from my own throat washing during my bout with influenza. That strain, named RI/5/57, became very useful to me and colleagues in the laboratory for many years, and also was used by investigators elsewhere. We used it in studies of the structure, absorption, penetration, replication, and assembly of the virus, including the isolation of and characterization of several previously unrecognized structural and nonstructural proteins of the virus.

In light of the origin of RI/5, it could be said that, to paraphrase David Tyrrell's words in the Foreword to the First Edition of the Textbook of Virology mentioned above, these studies in our laboratory went from bed to bedside to basic molecular biology.

Purnell W. Choppin

President Emeritus

Howard Hughes Medical Institute

Chevy Chase, MD, USA

Preface to the second edition

The second edition of the Textbook of Influenza has been completely revised and reflects the integration of disciplines concerning the emergence, evolution, pathogenesis, and control of influenza viruses in the field of veterinary and human public health with growing acceptance of the “One World–One Health” concept. This is reflected in consolidation of cross-disciplinary interests with a reduction in the number of chapters from 41 in the first Textbook of Influenza to 29 chapters in the current edition. Additionally, co-authorship of chapters by experts from complementary disciplines provides new insight. The textbook is aimed at students, researchers, and decision-makers across the “One Health” spectrum including ecologists, clinical and basic scientists, molecular and structural virologists, immunologists, public health officials, economists, and global pandemic control planners.

As predicted in the first Textbook of Influenza, the world has experienced another pandemic of influenza – the H1N1 pandemic of 2009. What was not predicted was that the pandemic would be caused by a subtype (H1N1) already circulating in the human population. This edition of the textbook examines the lessons learned and deals with the state of knowledge of many yet unresolved issues of severity and pathogenesis to improve preparation for future pandemics.

The advances in influenza genomics and reverse genetics now permits reconstruction of influenza viruses such as the 1918 Spanish influenza, and provides unique insight into innate immune-based pathogenesis. These strategies also permit studies on the interplay between the virus and the host, with potential for development of novel control strategies. They also bring us face to face with the future where we have the potential to generate influenza viruses that may or may not exist in nature. The textbook provides the background to these advances and the experiments that raise the issue of dual-use research of concern (DURC). The textbook does not attempt to resolve these issues, for resolution of these important issues were ongoing at the time of writing.

The text is divided in to eight sections: 1 A perspective on influenza; 2 Virus structure and replication; 3 Evolution and ecology; 4 Epidemiology and surveillance; 5 Immunology; 6 Vaccines and vaccine development; 7 Antivirals and 8 The outbreak of H7N9.

In the 15 years since publication of the first edition major advances have been made in each of these areas. The chapters in each of these sections are co-authored by leading influenza experts and are original contributions. Because of the desire to keep chapters concise the number of references has been restricted and authors have covered the major contributions in each field, but these are by no means all inclusive. The extent of overlap between chapters is limited and reflects different perspectives on each topic.

A very exciting advance in the section on vaccine development is understanding the molecular basis of antibody cross-reactivity between all of the known influenza hemagglutinin subtypes. These cross-reactive epitopes located in the stalk and receptor binding domains of the hemagglutinin molecule offer the possibility of a universal vaccine – the “Holy Grail” of influenza vaccinologists. The continued circulation and evolution of highly pathogenic H5N1 avian influenza in multiple endemic sites in Eurasia with sporadic spillover into humans and other mammals is a continuing threat to veterinary and human public health. The persistence of the highly pathogenic H5N1 virus in the wild bird reservoir is an unresolved question as is the potential for acquisition of human-to-human transmissibility. The H1, H2, and H3 subtypes are the only subtypes in the past century that have established stable lineages in humans, raising the possibility that only these subtypes can infect humans. However, it is wise to remember that all subtypes of influenza A that become established in mammals emerge from natural reservoirs including the stable H7N7 lineage that infected horses.

History has repeated itself. As was the case during production of the first edition of this textbook, a novel avian H7N9 influenza virus with high virulence for humans emerged in Asia as the second edition was going to press. Proving once again, influenza will continue to challenge us not only as scientists but also as authors. To that end, we have added an Appendix on H7N9 influenza that provides the available preliminary information to meet these challenges.

Robert G. Webster

Arnold S. Monto

Thomas J. Braciale

Robert A. Lamb

Acknowledgments

The contributing authors of the second edition of the Textbook of Influenza are the real heroes of this project; they are all extremely busy people but they found the time to make this book what was envisioned – a textbook at the cutting edge of knowledge. We are extremely grateful to every one of the authors and say thank you for a job superbly done. We thank the entire staff of Wiley Blackwell involved in this project, from the initial meeting with Maria Kahn over a cup of tea at The Royal Society for accepting the need for a second edition of the textbook. Rebecca Huxley, Aileen Castell, Claire Brewer, Kate Newell, Lucinda Yeates, and Deidre Berry all played important parts in bringing the book to completion, especially Elisabeth Dodds who handled the entire submission process and Jan East for careful copyediting and adding the final touches. We are especially pleased with the acceptance of the need for color illustrations throughout. Purnell Choppin provides personal insight into influenza in his foreword and James Knowles (St. Jude), Shawn Wood (University of Virginia), Susan H. Dara (University of Michigan), and Barbara St. Cyr (Northwestern University) provided outstanding administrative assistance throughout the project with continuing communication between the authors, editors, and publishing staff. We acknowledge the support of our institutions and funding agencies which are given at the end of each chapter and most importantly we thank our wives, Marjorie Webster, Reay Paterson (Lamb), Ellyne P. Monto, and families for their support and encouragement.

Robert G. Webster

Arnold S. Monto

Thomas J. Braciale

Robert A. Lamb

Any views expressed in the Work by contributors employed by the United States government at the time of writing do not necessarily represent the views of the United States government, and the contributor's contribution to the Work is not meant to serve as an official endorsement of any statement to the extent that such statement may conflict with any official position of the United States government.

PART 1

Influenza: Perspective

Section Editor: Robert G. Webster

1

Human influenza: One health, one world

Daniel B. Jernigan and Nancy J. Cox

National Center for Immunization and Respiratory Diseases, Influenza Division, Centers for Disease Control and Prevention Atlanta, GA, USA

Introduction

Influenza viruses know no boundaries, circulating within species and occasionally jumping between them, causing infections around the globe. The impact of influenza is also wide-ranging, and the growing interconnectedness and complexity of the world presents an increasing challenge to influenza prevention and control. As people and the animals that support them increase in numbers and interactions, the opportunities for virus adaptation and cross-species transmission increases as well. An undetected exchange of viruses among humans and animals in a rural village may eventually manifest as a global pandemic. Within this interconnected context, opportunities are also emerging for coordinated, collaborative, innovative, and integrated efforts to focus new technologies and approaches in a shared response to the global challenges of influenza.

Global impact of influenza

Influenza causes significant human illness and death each year. The actual global impact of seasonal influenza is difficult to determine due to incomplete surveillance data; however, the World Health Organization (WHO) has estimated that around 1 billion cases of seasonal influenza infection occur each year, with around 3–5 million cases of severe illness, and 300 000–500 000 deaths [1]. The global financial costs of seasonal influenza are also not well known. In the United States, where data collection is robust, estimates of the costs of influenza have been reported to be an average of $10.4 billion per year for direct medical costs and $87.1 billion for the total economic burden of annual influenza epidemics [2].