Biochemical genetic analysis of 2',3'-dideoxyadenosine metabolism in human T lymphocytes

2',3'-dideoxyadenosine (ddAdo) has been shown to inhibit the infection of cultured human T lymphoblasts with the human immunodeficiency virus-1 (HIV-1). However, the pathways of ddAdo metabolism in T lymphocytes have not been well defined. We have studied the uptake and degradation of ddAdo in human CEM T lymphoblasts, in mutant CEM T cells deficient in adenosine kinase or deoxycytidine kinase, and in normal lymphocytes and monocytes. The results indicate that ddAdo may be phosphorylated in T cells by several different enzymes, although deoxycytidine kinase predominates. However, 99% of the ddAMP formed is deaminated by AMP deaminase and subsequently dephosphorylated. Thus, the ability of ddAdo to prevent HIV-1 infection may be limited in cells with high AMP deaminase activity.