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
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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
1
Human influenza: One health, one world
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.
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].
Influenza infection in birds and other animals also has a substantial impact. Since the detection and reporting of highly pathogenic avian influenza (HPAI) A (H5N1) epidemics in 1997, the virus has spread globally with hundreds of millions of birds dying from illness or culling. Costs for the international response since 2003 have been estimated to be at least $2 billion [3]. The presence of ongoing outbreaks in South-East Asia has damaged trade potential and has shifted exporting of poultry away to other nonaffected regions. For resource-challenged communities in HPAI H5N1 endemic regions, the loss of protein nutrition from decimated domestic flocks and the drop in income from lost poultry sales is significant. Swine are also infected by influenza viruses, but the burden of illness and death for swine is considerably less than that seen for HPAI viruses in domestic poultry. Influenza illness in swine is often considered by pork producers to have considerably less of an impact on production than on the potential downside for pork consumption and global export which might be prompted by public concerns about swine influenza infecting people. From a human health perspective, the greatest impact of influenza from swine and birds is their important role as sources of novel influenza viruses capable of causing pandemics.
In the last 100 years, there have been four instances where influenza viruses with genes originating from avian or swine reservoirs emerged (either with or without reassortment with human influenza viruses) with sustained, efficient, human-to-human transmission, spreading around the world [4]. The impact from these pandemics has been substantial, most notably with the 1918 H1N1 virus. It has been estimated that, globally, there were around 50 million human deaths due to infection with the 1918 pandemic virus [5]. Estimates of the 2009 pandemic were substantially lower, with 151 700–575 400 deaths globally [6]. If a severe pandemic were to arise from the H5N1 virus, the World Bank has estimated a cost of up to three trillion dollars [7]. For past pandemic viruses, it is not known exactly where or when the interchange of virus occurred from swine or bird to humans, but the subsequent impact from these pandemics was extensive. What are the factors that contribute to emergence of these viruses? What can be done for early detection and prevention?