The xenotropic murine leukemia virus-related virus (XMRV) is a human retrovirus, recently isolated from tissues of prostate cancer patients with impaired RNase L activity. In this study, we evaluated 10 licensed anti-HIV-1 compounds for their activity against XMRV, including protease inhibitors (PI), nucleoside reverse transcriptase (RT) inhibitors (NRTI), non-nucleoside RT inhibitors (NNRTI) and an integrase inhibitor. No PI affected XMRV production; even high concentrations of Ritonavir failed to inhibit the maturation of XMRV Gag polyproteins. Among the NRTI, NNRTI and integrase inhibitors used in this study, only AZT blocked XMRV infection and replication through inhibition of viral reverse transcription. This sensitivity of XMRV to AZT may be explained by the modest homology in the motif D sequences of HIV-1 and XMRV reverse transcriptases. If XMRV becomes established as an etiological agent for prostate cancer or other diseases, AZT may be useful for preventing or treating XMRV infections in humans.
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