Genetic Variation Among Influenza Viruses

Genetic Variation Among Influenza Viruses documents the proceedings of ICN-UCLA symposium held in Salt Lake City, Utah, 8-13 March 1981. The symposium brought together people from different disciplines working with the common objective of reducing the ravages of influenza and to expose them to the totality of the problem of influenza. The papers presented at the meeting included nearly all major aspects of influenza in which important advances are being made. Because of recombinant DNA technology and rapid DNA sequencing, a number of genes of influenza virus from a number of strains have been either completely or partially sequenced. Among these, the gene coding for hemagglutinin (HA) has been most intensively studied and the HA of one or more strains from each subtype (H1, H2, H3) has been completely sequenced. Other topics discussed include the question of drift and shift at the genomic level; the role of the capped host mRNA is the process of initiation of transcription; and the regulation of viral transcription. This volume also includes papers presented by the speakers of the plenary sessions and that of keynote speaker, Sir Charles Stuart-Harris as well as the selected papers presented in the poster sessions.

With the advent of genetic engineering methods and improved biochemical tech niques, much has been learned about the replication of influenza viruses, their structure and their epidemiology. It appears that the time is ripe to review these efforts and to provide a molecular perspective of influenza virology. It is hoped that this book will stimulate our thinking, help us in designing new experiments, and possibly show avenues leading to the control of the diseases associated with influenza viruses. Peter Palese, New York, N. Y. August 1983 David W. Kingsbury, Memphis, Tenn. Contents List of Contributors. . . . . . . . . . . . . . . . . XV 1. The Evolution of Influenza Viral Genetics - A Perspective. By E. D. Kilbourne. . . . . . . . . . . . . . . . 1 I. Introduction. . . . . . . . . . . . . . . . . 1 II. The Development of Modern Influenza Viral Genetics 2 A. Early Evidence of Genetic Variation in the Laboratory 2 B. Application of Formal Genetic Techniques to Studies of Influenza Virus . . . . . . . 3 C. Genetic Markers. . . . . . . . . 3 D. Development of Plaquing Systems. . . 4 E. The Use of Conditional Lethal Mutants 5 F. New Approaches in Influenza Virus Genetics. 6 1. The Biochemical Identification of Viral Gene Products in the Unambiguous Definition of Viral Inheritance . . . 6 2. Mapping of the Influenza Virus Genome by Correlative Physico-Chemical and Biological Techniques. . . . . . 7 3. The Application of Molecular Biological Techniques to the Study of Viral Genetic Variation. . . . . . . . . 8 4. Oligonucleotide Mapping of Viral RNA's . . . . . . . 8 5. Contribution of Protein and RNA Sequencing to Influenza Viral Genetics-Intragenic Mapping . . . . . . . 8 III. Viral Genetics and the Understanding of Viral Virulence and Pathogenicity . . . . . . . . . . . . . . . . . . .

Public health officials and organizations around the world remain on high alert because of increasing concerns about the prospect of an influenza pandemic, which many experts believe to be inevitable. Moreover, recent problems with the availability and strain-specificity of vaccine for annual flu epidemics in some countries and the rise of pandemic strains of avian flu in disparate geographic regions have alarmed experts about the world's ability to prevent or contain a human pandemic. The workshop summary, The Threat of Pandemic Influenza: Are We Ready? addresses these urgent concerns. The report describes what steps the United States and other countries have taken thus far to prepare for the next outbreak of "killer flu." It also looks at gaps in readiness, including hospitals' inability to absorb a surge of patients and many nations' incapacity to monitor and detect flu outbreaks. The report points to the need for international agreements to share flu vaccine and antiviral stockpiles to ensure that the 88 percent of nations that cannot manufacture or stockpile these products have access to them. It chronicles the toll of the H5N1 strain of avian flu currently circulating among poultry in many parts of Asia, which now accounts for the culling of millions of birds and the death of at least 50 persons. And it compares the costs of preparations with the costs of illness and death that could arise during an outbreak.

With the growing global fear of a major pandemic, avian influenza (AI) virus research has greatly increased in importance. In Avian Influenza Virus, an expert team of researchers and diagnosticians examine the fundamental, yet essential, virological methods for AI virus research and diagnostics as well as some of the newest molecular procedures currently used for basic and applied research. They present exciting, cutting-edge new methods that focus both on studying the virus itself and on work with avian hosts, an area greatly lacking in research.

My lifetime encompasses the postwar subsidence in the early 1920s of the greatest influenza pandemic in history, direct encounters with FM1 virus at Fort Mon mouth in 1947, the care of influenza patients in the 1950s, the pursuit of the in fluenza virus through the modern pandemics of 1957 and 1968, and a present in which the genes of the virus have dissembled in the DNA of vaccinia virus and Escherichia coli through the wand of "high tech. " If my corpus could be fossilized for archival and archaeological purposes, it would be found to contain immune cells branded with the imprint of the "swine" influenza virus of post-1918 and brain cells no less imprinted with memories of the abortive return of its descendant during America's bicentennial. But before that unlikely event, I wanted to try to make some sense out of this baffling dis ease and its viruses-expecting no definitive revelations but hoping for a sharper definition of problems. Hence this book. It is an audacious act in these days of specialization to essay a book such as this singlehandedly, but I have done so for selfish reasons. I wanted to reexam ine old questions about the nature of influenza and its epidemics in the light of the dazzling advances in molecular biology of the past few years. No virus has been better studied, but few diseases are less well understood.

The topic of antigenic variation is important in both biology and medicine. It is of enormous interest, as it describes the process(es) whereby microorganisms 'shift shape', by genetic rearrangement or otherwise. In medical terms, this has a major impact on the infectious disease process, since the immune system has great difficulty in keeping up with this variation, and thus eliminating the infectious agent. Antigenic variation is a major method by which microbes evade the immune response, and persist in the body. The broad scope of the book appeals to all those working in the field of infectious disease, immunology of infection, pathogenesis, molecular biology and also to evolutionary biologists. Topics covered include not only bacterial species, and viruses such as influenza, HIV, Rotavirus, but also eukaryotic parasites - one of the most fascinating groups of organisms exhibiting this behaviour. Comprehensive coverage of antigenic variation from viruses to parasites Discussions devoted to molecular mechanisms of host evasion Detailed descriptions of host/pathogen interactions