Susceptibility of the Human Retrovirus XMRV to Antiretroviral Inhibitors

Robert A Smith; Geoffrey S Gottlieb; A Dusty Miller

Disclosures

Retrovirology. 2010;7(70) 

In This Article

Conclusions

Our analysis demonstrates that XMRV is sensitive to a broader range of NRTIs than was previously appreciated; these include analogs that are used in the clinical treatment of HIV-1 infection (AZT and tenofovir) as well as other structurally-related NRTIs (AZddA, AZddG and adefovir). We observed a distinct pattern of NRTI sensitivity in XMRV that correlates with the structure of the pseudosugar moiety; while XMRV is sensitive to 3'-azido nucleoside analogs and acyclic nucleoside phosphonates, the virus is moderately resistant to dideoxynucleosides and highly resistant to L-form thiacytidine NRTIs. Importantly, this pattern suggests that other 3'-azido or acyclic nucleoside analogs might also exhibit anti-XMRV activity. In addition, our data show that elvitegravir blocks XMRV infection with a degree of potency similar to that of AZT. This finding expands the number of integrase inhibitors with known activity against XMRV in vitro.

While our use of the same target cell type for XMRV and HIV-1 provides an important reference point for characterizing XMRV drug susceptibility, we note that the two viruses utilize different receptors for entry and are therefore likely to infect differing host cell types in vivo. Ultimately, the clinical utility of antiretrovirals for XMRV will depend on drug distribution and metabolism at anatomic sites of XMRV replication, the degree to which antiretrovirals reduce XMRV viral load, and whether reductions in viral load slow pathogenesis. In the event that XMRV is shown to be the causative agent of human disease, our data identify candidate drugs for clinical studies of antiretroviral therapy in XMRV-infected patients.

Comments

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