Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors.

Abstract

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Robert A Smith, Geoffrey S Gottlieb, A Dusty Miller
• Journal: Retrovirology (Retrovirology) Vol. 7 Pg. 70 (Aug 31 2010) ISSN: 1742-4690 [Electronic] England
• PMID: 20807431 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Retroviral Agents

Topics

• Anti-Retroviral Agents (pharmacology)
• Drug Resistance, Viral
• Gammaretrovirus (drug effects)
• HIV-1 (drug effects)
• Humans
• Inhibitory Concentration 50
• Microbial Sensitivity Tests (methods)
• Virus Replication (drug effects)