Which host genes abrogate immunity to chronic infections?
Some host genes regulating T cell mediated viral clearance
Current therapies have had a tremendous impact on chronic viral infections and diseases like HIV and hepatitis C but these treatments are rarely curative. A major obstacle is the high mutation rate of these organisms, which renders them refractory to treatments that directly target their viability. One of the greatest challenges is developing treatments that cure these diseases and that are impervious to resistance mechanisms used by the pathogens to escape eradication. We focus our attention on modulating immune responses in mouse models of chronic viral infection to promote viral clearance. Targeting host molecular pathways, which the pathogen is dependent on for persistence, rather than viral proteins, circumvents a major resistance mechanism. Using an array of conditionally gene targeted mice we can interrogate the relevance of many genes implicated in immune regulation and test their relevance in immunity to persistent pathogens. We aim to identify host pathways that upon manipulation will permit clearance of persistent pathogens. These studies are particularly relevant to HIV infections where the immune system fails to clear virus and eventually succumbs to uncontrolled viral turnover.