Influenza: viral determinants of the pathogenicity and epidemicity of an invariant disease of variable occurrence.

If influenza is a riddle wrapped in mystery inside an enigma, then the viral genes are the riddle, the variable surface antigens for which they code are the mystery, and the course and cause of epidemics the ultimate enigma. Paradoxically, the disease itself has remained a stable and recognizable entity through the years, whether initiated by A/PR/8/34 or A/USSR/90/77 variant viruses. Thus, evolution appears to have preserved the disease but not the virus. Among the questions before us are: (1) Have we become obsessed with differences instead of similarities, and have we overemphasized minor differences in viral (antigenic) structure as epidemic determinants? (2) To what extent do viral antigens reflect selection by population antibody? (3) To what extent is antigenic change the pleiotropic consequence of protein structural alteration for purposes other than escape from specific neutralization? These and other questions are discussed in relating viral form to function.