Early Differential IDO Expression Patterns In The MAIDS Model
Date
2012-05-10
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Abstract
Murine acquired immunodeficiency syndrome (MAIDS) is an animal model that is used to study AIDS. It is caused by an exposure to a defective retrovirus present in the LP-BM5 isolate of murine leukemia virus (MuLV) mixture. Strains of inbred mice differ in their resistance to MAIDS development. While susceptible strains of mice such as C57BL/6 develop progressive immune deficiency, other resistant strains such as BALB/c recover from infection and build protective immunity. Earlier studies, conducted in the MAIDS model system, indicate that knocking down or inhibiting enzymatic activities of indoleamine 2, 3-dioxygenease (IDO) suppresses viral replication, up-regulates Type I IFN mRNA levels, and increases plasmacytoid dendritic cell counts. Since IDO is a natural immunosuppressant molecule, its overactivation could contribute towards immune dysregulation and disease progression in MAIDS susceptible mice. Preliminary experiments conducted in our lab showed significantly higher IDO mRNA expression levels in the secondary lymphoid organs of naïve and virus-infected disease-susceptible C57BL/6 mice than in resistant BALB/c mice. In this project, we developed our own ELISA based assay to measure mouse-IDO. Our results show an early upregulation of IDO protein following viral exposure, where differences of protein expression between the two strains of mice are highly pronounced 14-days post infection both in the spleen and lymph nodes of the animals. IDO-mediated immune activity in the susceptible C57BL/6 strain may perpetuate viral replication by dampening efficient immune anti-viral responses. Pilot experiments are being conducted to elucidate immune mechanisms that could mediate this MuLV-induced increase of IDO expression, such as immunoinhibitory CTLA-4/B7 interactions.
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HIV/AIDS, MAIDS, MuLV, IDO, Immunosuppression