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Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors - Source: Retrovirology, Aug 31, 2010

  [ 12 votes ]   [ Discuss This Article ]
By Robert A Smith, et al. • • August 31, 2010

[Note: the full text of this article is available free at]

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:]

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