Infection with various viruses leads to vigorous stimulation of the immune system and the elicitation of specific anti-viral responses. In addition, viruses and their products often alter the normal biology of infected cells. The goal of this project is to understand the signaling pathways that are affected by virus infection with an emphasis on murine leukemia viruses. Previous studies of mice infected with retroviruses that cause an immunodeficiency syndrome, MAIDs, showed that expression of interferon (IFN) gamma was critical to disease progression and that T cells from infected mice expressed high levels of transcripts for the transcriptional regulator, Gfi-1. To understand the contributions of IFN to MAIDS, we have studied mice deficient in IFN signaling due to a knockout of the ICSB gene. We have shown that ICSBP is crucial mediator of resistance to some infectious agents and that it plays a major role in regulating mhelopoiesis. In addition, mice defective in ICSBP expression develop a disease with similarities to chronic myelogenous leukemia (CML) in humans. Preliminary studies suggest that cells from patients with CML have reduced expression of ICSBP. Mice expressing Gfi-1 as a transgene have been produced and are under study.
