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Viruses were first discovered and recognised as a separate class of microbes around the turn of the century. They were studied because they were found to be agents of some of the most important diseases of plants and animals, but because of their submicroscopic size and requirement to replicate within living cells it was not until the 1950s that virology became firmly established as a branch of science in its own right. At that time methods for cell culture and virus purification were developed, and the introduction of negative staining allowed electron microscopists to visualise the structures of viruses for the first time. The establishment of cell culture systems enabled studies of the replication of animal viruses and the development of attenuated live vaccines against important human pathogens such as measles, rubella and poliomyelitis. In the following twenty five years, virology made major contributions to the fields of cell and molecular biology and molecular genetics. Concepts arising directly from the study of animal virus replication include capping and polyadenylation of messenger RNAs, introns in cell DNA and splicing of RNA transcripts, interferons, reverse transcription, cellular oncogenes and the intracellular processing and presentation of antigens at the cell surface. Our knowledge of virus structure and replication has increased in complexity, and so have the techniques required for virus detection, characterisation and diagnosis. The ability to sequence virus nucleic acids, whether DNA or RNA, by relatively simple technologies involving the polymerase chain reaction has led to our ability to trace virus movements in human or animal populations with great precision. A new field of molecular epidemiology has opened up and is providing the basis for World Health Organisation (WHO) campaigns to eradicate poliomyelitis and measles over the next five years. In addition, this genetic sequence information is being used as the basis for the rational design of new antiviral drugs as well as vaccines. To help cope with the increased range and complexity of methods required for the study of viruses, we have assembled the present volume which aims to provide scientists working in clinical or research laboratories with clear descriptions and protocols of the most up-to-date, definitive techniques in virology. All the chapters are written by experts who have first-hand knowledge and experience of the methods they describe. We have divided the subject up into classical, molecular, and medical virology for convenience; these divisions are merely meant to guide the reader and are not intended to be exclusive. The chapters in Section 3 overlap somewhat in subject matter with those in Sections 1 and 2, but are written from the perspective of the medical virologist and provide additional insights that are important in the clinical setting when studying virus diseases. We have included a number of appendices that may be used as a convenient information source on various aspects of virology. In each case reference to more substantial texts is made in the appendix, and these should be consulted if more detail is required. The overall size and complexity of this volume was limited by our desire to create a useful methods book that would be affordable to most virologists. We would have achieved our aims if the book ends up in frequent use in the laboratory, not merely in the library. We are grateful to Academic Press, especially to Tessa Picknett, for their patience and considerable professional input. BRIAN WJ MANY HILLAR O KANGRO JUNE 1995