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Background: XMRV (xenotropic murine leukemia virus-related virus) is the first known example of an exogenous gammaretrovirus that can infect humans.
A limited number of reports suggest that XMRV is intrinsically resistant to many of the antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small subset of these inhibitors. In the present study, we used a novel marker transfer assay to directly compare the antiviral drug sensitivities of XMRV and HIV-1 under identical conditions in the same host cell type.
We extend the findings of previous studies by showing that, in addition to AZT and tenofovir, XMRV and HIV-1 are equally sensitive to:
• AZddA (3'-azido-2',3'-dideoxyadenosine),
• AZddG (3'-azido-2',3'-dideoxyguanosine),
• And adefovir.
These results indicate that specific 3'-azido or acyclic nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT) also block XMRV infection with comparable efficacy in vitro.
Our data confirm that XMRV is highly resistant to the non-nucleoside RT inhibitors nevirapine and efavirenz and to inhibitors of HIV-1 protease.
In addition, we show that the integrase inhibitors raltegravir and elvitegravir are active against XMRV, with EC50 values in the nanomolar range.
Our analysis demonstrates that XMRV exhibits a distinct pattern of nucleoside analog susceptibility that correlates with the structure of the pseudosugar moiety and that XMRV is sensitive to a broader range of antiretroviral drugs than has previously been reported.
We suggest that the divergent drug sensitivity profiles of XMRV and HIV-1 are partially explained by specific amino acid differences in their respective protease, RT and integrase sequences.
Our data provide a basis for choosing specific antiretroviral drugs for clinical studies in XMRV-infected patients.
Source: Retrovirology, Aug 31, 2010;7:70. doi:10.1186/1742-4690-7-70Smith RA, Gottleib GS, Miller AD. Department of Pathology and Department of Medicine, University of Washington, Seattle; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [Email: firstname.lastname@example.org]