Orthomyxdviridae

Properties of Orthomyioviridae 489

Pathogenesis and Itmriumty 493

Clinical Features of Influenza 494

Laboratory Diagnosis.!.____494

Epidemiology 495

Control 496 i

Further Reading 499

Few viruses have played a more central role in the historical development of virology than that of influenza. The pandemic that swept the world in 1918, just as the First World War ended, killed 20 million people—more than the war itself. The eventual isolation of the virus in ferrets in 1933 was a milestone in the development of virology as a laboratory science. During the ensuing two decades Burnet pioneered technological and conceptual approaches to the study of the virus in embryonated eggs. His system became the accepted laboratory model for the investigation of viral multiplication and genetic interactions until the early 1950s, when newly discovered cell culture techniques transferred the advantage to poliovirus. Hemagglutination, discovered accidentally by Hirst when he tore a blood vessel while harvesting influenza-infected chick allantoic fluid, provided a simple assay method, subsequently extended to many other viruses. The imaginative investigations of Webster and Laver into the continuing evolution of influenza virus by antigenic drift and shift established the discipline of molecular epidemiology. The pièce de résistance was the description by Wiley, Wilson, and Skehel of the location of the antigenic sites on a three-dimensional model of the influenza HA molecule derived by X-ray crystallography (see Fig. 4-3).

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