Research has been initiated to determine the adenovirus gene products required for cell damage and to establish the molecular mechanisms effecting the pathogenesis of adenovirus diseases. The cotton rat is an ideal animal model for these studies because the pathology of the pneumonia and upper respiratory disease produced by type 5 adenovirus in this animal is similar to that observed in humans. Basic experiments have been carried out to establish the parameters of the infection: kinetics of viral replication and clearance of virus from the lung; the temporal relationship of viral replication to the development of pneumonia; the cellular sites of viral replication in the lung; the immune response to infection; and the establishment of viral latency. Two species of cotton rats, Sigmadon hispidus and Sigmadon fulviventir, were compared in these studies; the S. hispidus proved to be the better species for investigating pathogenesis of pneumonia, but the S. fulviventir, appears to have distinct advantages for studies of the latent state. Experiments have been initiated using a variety of deletion, insertion, and conditionally lethal mutants in an effort to determine the gene product or gene products responsible for cell damage and subsequent development of pneumonia. An adenovirus expression vector, using the vaccine strain of type 4 adenovirus, is being constructed to develop an alternate viral vaccine containing the rotavirus gene encoding the major antigen that induces neutralizing Abs. This vaccine would have a number of advantage for prevention of rotavirus infections throughout the world.
