INTRODUCTION

Influenza virus is one of the most enigmatic of human viruses. The virus was one of the first human viruses to be isolated – in 1933, by Andrewes, Laidlaw and Smith. The vaccine, developed in the early 1940s, is one of the first human vaccines. From earliest times influenza lent itself to be intensively studied. Human volunteer studies and detailed investigations of its pathogenesis and immunology were carried out as early as the 1950s. In addition, a variety of animals and avian species have been valuable models to study the virus-host interactions in great detail. Yet despite all of this, important gaps in our knowledge of this mysterious virus remain. A vast treasure trove of knowledge about influenza virus has accumulated over the decades, however, and has greatly enriched our understanding of virushost interactions, viral immunity, vaccine design and in particular molecular mechanisms of how viruses have so successfully evaded the body's immune responses. Influenza virus can, in fact, be described the paradigm illustrating the relationship between genetics, molecular structure, immunology and epidemiology.

Influenza virus is widely distributed among avian and mammalian species, with man being a relatively recent host. In humans, influenza is estimated to be directly responsible for over 250 000 deaths annually. Indirectly the burden of disease is far wider, as influenza often triggers complications such as cardiovascular disease, bacterial pneumonia and metabolic disease. Essentially a disease of the cold winter months (and in the tropics predominantly the rainy season) the virus regularly infects about 15–30% of the population annually over a period of 6–12 weeks. Some seasons are more severe than others, severity mainly being related to the more extensive antigenic changes in the haemagglutinin protein of the virus (see below). Every two to three times a century there is a major change in the virus, either due to viruses crossing the species barrier from birds to other mammals including humans or to genes coding for the haemagglutinin, and sometimes also due to the neuraminidase being imported into human viruses from an avian or mammalian source by a process called reassortment.