Wounding the Immune System with its Own Blade: HIV-Induced Tryptophan Catabolism and Pathogenesis

Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme which plays a key role in maintaining the physiologic immune balance between the efficient responses to insulting pathogens and the control of harmful autoimmune reactions. During HIV infection, multiple mechanisms involving both viral and cellular components, contribute to enhance IDO expression and activity in an uncontrolled manner. The downstream effects of IDO overactivation collectively contribute to the immune alterations which characterize HIV disease. This review explores the cellular and molecular pathways which result in IDO upregulation during HIV infection and considers the consequences of IDO hyperactivity on the immune system, their relevance in the context of HIV immunopathogenesis and the potential for specific therapeutic intervention.