Molecular Genetics of the Pathogen-Host Interaction, Mechanism of Mucosal Immunity
Research has focused on understanding cellular and molecular aspects of viral infection in the GI tract and liver using reovirus. This work has led to the development of an exciting technology to sort out cellular genes that participate in cellular infection. Gene-trap retroviruses are used to select cells that are resistant to lytic reovirus infection. One hundred twenty cell lines have been established with a reovirus resistant phenotype and the genes disrupted are being characterized. Of the 120 genes disrupted, 20 of the genes are known. Many of these known genes are part of the endocytic pathway and 50% have been associated with virus infections. This work has been expanded to include the study of cellular genes involved in Trypanosoma cruzi infection. In addition, the laboratory is currently pursuing studies to elucidate the mechanisms of generating effective mucosal immunity. Recent studies have found that there is an oligoclonal response of the host to reovirus and that mucosal CD8+ that express the aa homodimer do not signal via NfkB.