GENETICALLY CONTROLLED RESISTANCE TO VIRUSES Margo A. Brinton Wistar Institute Philadelphia, PA 19104 INTRODUCTION Historically, the first demonstrations of the existence of host genes that could control resistance to disease induced by an animal virus were reported independently by Lynch and Hughes (1) and Webster and Clow (2) in 1936. Subsequently, a number of other genes have been identified in various strains of inbred mice, each of which confers resistance to a specific type of virus infection (3,4,5). Since different families of viruses vary greatly in their modes of replication, it would be expected priori that the various resistance gene products would also differ in their mechanisms of action. Host resistance genes may act on a particular virus infection at the level of receptors, intra- cellular replication, interferon inhibition, or the immune response. A host resistance gene can therefore be an important component in determining the outcome of a particular virus infection. However, the severity of a virus-induced disease is the result of the interaction between host resistance genes, viral virulence genes, and the host defense system. MURINE GENES INFLUENCING DISEASE INDUCED BY VIRUSES The majority of studies of genetic resistance have been carried out in various strains of inbred mice. Identification of an increasing number of host genes controlling the specific virus infections in inbred mice as well as in some wild popula- tions (6) indicates the importance of such genetic effects. Genes which modulate disease induced by nine different families of RNA and DNA viruses in mice have thus far been identified. Among the 475 T. K. Eisenstein et al. (eds.), Host Defenses to Intracellular Pathogens © Plenum Press, New York 1983