For the past 20 years or more, retroviruses have proven to be highly rewarding objects of study, and have provided new and important insights into fundamental aspects of eukaryotic molecular biology, gene organization, genetics, and oncogenesis. The goal of this proposal is to continue our studies in several key areas of molecular retrovirology emphasizing avian and murine retroviral models. Areas of emphasis include the following: 1) The structure and function of ALV env proteins and their receptors as well as mechanisms of viral entry and superinfection resistance; 2) The specificity and mechanism of viral DNA integration and the role of DNA structure and DNA-associated proteins in this process; 3) The mechanisms underlying the extraordinary genetic and biological diversity characteristic of retroviruses, including mechanisms of legitimate and illegitimate recombination and the role and power of selective influences in molding the viral genome; 4) The evolution of endogenous retroviruses and the use of these elements to study genetics and evolution of their hosts; 5) The role of superantigen activity in the replication of MMTV and the evolution of these viruses and their host.
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