Shows a Unique Combination of a Phosphorylation Defect and Increased Efflux of the Agent

9-(2-Phosphonylmethoxyethyl)adenine (PMEA) is a new antiviral agent with activity against herpes viruses and retroviruses, in-cluding human immunodeficiency virus, but its metabolism and mechanism of action remain unclear. We have isolated a human I Iymphoid cell line (CEMr-1) that is resistant to the antiprolifer-ative effects of PMEA. The antiviral effects of PMEA against human immunodeficiency virus-i infection were also greatly re-duced in GEM-ri cells, compared with the parental cells. This mutant showed cross-resistance to the related acyclic nucleoside phosphonates 9-(2-phosphonylmethoxyethyl)diaminopunne and 9-(2-phosphonylmethoxyethyl)guanine and the Iipophilic prodrug bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine-(bispom-PMEA), as well as partial resistance to the punne nude-osides 2-chlorodeoxyadenosine, 2-fluro-9-3-o-arabinosylfurano-syladenine, and adenosine, but did not show resistance t