HIV drugs could treat prostate cancer and CFS – if they are caused by XMRV

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The retrovirus, xenotropic murine leukemia virus-related virus (XMRV), has been – controversially – linked to both prostate cancer and chronic fatigue syndrome (CFS). In an attempt to clarify the association of XMRV with disease, researchers at Emory University are developing a serum-based assay to detect neutralising antibodies to the virus which should begin to answer basic questions about how widespread the virus is, and how it is transmitted. The team found good agreement between their serum based assay and polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) tests carried out on prostate samples from cancer patients, and showed that at least some of the patients had been infected with XMRV. The study is published in the April issue of Urology.

Meanwhile, other researchers at Emory University/Atlanta Veterans Affairs Medical Center and the University of Utah have been looking for ways to treat XMRV should it turn out to have a causal role in prostate cancer or chronic fatigue syndrome. The team evaluated 45 compounds, mostly drugs approved for the treatment of HIV/AIDS, and found that four of them were able to inhibit XMRV with EC50 values of < 1µM. XMRV replication was studied in both MCF-7 cells (generated from human breast cancer) and LNCaP cells (generated from human prostate cancer). The most effective compounds were two nucleoside reverse transcriptase inhibitors (zidovudine and tenofovir disoproxil fumarate) and two integrase inhibitors (raltegravir and L-000870812). Despite the lack of homology (only 14% identity) between HIV-1 integrase and XMRV integrase, raltegravir showed particularly good activity against XMRV with EC50 values of 0.005µM and 0.03µM in MCF-7 and LNCaP cells respectively (cf 0.001µM for HIV-1 grown in PBMCs). The EC90/EC50 ratio was significantly higher for XMRV grown in MCF-7 cells than for XMRV grown in LNCaP cells or for HIV-1 grown in PBMCs (700, 15 and 9 respectively). Synergy studies were carried out in LNCaP cells: combinations of raltegravir and any of the other three compounds were found to act synergistically.

The authors hope that if XMRV is established as a cause of prostate cancer or CFS, existing HIV treatments may prove to be effective therapies for these conditions.

The study is published in PLoS ONE.

Retrovirus Linked to Chronic Fatigue Syndrome

Tired Man by József Somogyi Image: Wikimedia - Burrows
"Tired Man" by József Somogyi

Image: Wikimedia - Burrows

Xenotropic murine leukemia virus-related virus (XMRV) was in the news a month ago as researchers provided new evidence that the virus could contribute to the development of prostate cancer. Now, scientists have linked XMRV to Chronic Fatigue Syndrome (CFS).

Knowing that patients with CFS can share an immune system defect with prostate cancer sufferers, the team looked for XMRV in blood samples from patients with CSF. In the study, which is published in the journal Science, XMRV was detected in blood samples from 67% of CFS patients and in only 4% of samples from healthy individuals. The infected blood samples not only contained viral DNA but were shown to produce viral proteins and infectious viral particles. Retroviral particles were also detected in patient samples using transmission electron microscopy. The virus, which is transmitted through body fluids and is not airborne, was found to be transmitted by both cell-to-cell and cell-free mechanisms. Secondary viral infections could be established in uninfected primary lymphocytes by exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients.

The data demonstrate the first direct isolation of infectious XMRV from humans and raise the possibility that XMRV may be a contributing factor in CFS. Although the research provides a strong association between XMRV and CFS, it does not prove that XMRV causes CFS. If cause-and-effect is established, antiretroviral drugs could potentially be developed to treat CFS. Since the Science paper was submitted, the team have shown that 95% of plasma samples from CFS patients tested positive for XMRV antibodies. A clinically validated test to detect XMRV antibodies in plasma is currently under development, and the team plan to collect more data on the incidence of XMRV in the general population. The team are also investigating whether approved antiretroviral drugs are effective against XMRV and could benefit CFS patients.