Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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 <it>in vitro</it>. 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 EC₅₀values in the nanomolar range.</p> <p>Conclusions</p> <p>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.</p

Embedding implants in undergraduate dental education

This article represents the consensus from a meeting of the British Society of Prosthetic Dentistry's Education Group which met to discuss implant dentistry at the undergraduate dental student level. The consensus recognises the need to embed the teaching of implant supported prostheses if such a treatment modality is to be widely practised after graduation. This short article makes some recommendations as well as detailing some challenges and barriers that need to be overcome if implant dentistry is to be successfully embedded in an undergraduate dental curriculum