The overall objective of the proposed research is to study the mechanisms that allow the influenza virus to repeatedly produce new variants capable of causing widespread human disease. Questions that will be asked include: (1) To what extent are genes similar to those coding for the human influenza virus proteins found among the animal influenza strains? (2) Can correlations be made between biological properties of influenza virus strains and the presence of specific genetic information? (3) Can animal influenza virus strains be detected that have been preserved for long periods of time without extensive mutational change? (4) Is the mutation rate of an influenza strain genetically controlled by the virus, or is it influenced by the host cell in which it is grown? (5) Can intragenic recombinants be detected among existing influenza isolates or can they be selected by using the proper selective conditions? Genetic homologies will be measured by competitive RNA hybridization and by oligonucleotide mapping. Monoclonal antibodies will be used to quantitate mutations affecting individual antigenic determinants and to select for intragenic recombinants. These studies will provide information on the origin of new epidemic and pandemic influenza virus strains. It may also provide us with a more rational basis for assessing the biological potential of new virus strains.