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HIV drugs combat virus that might be linked to prostate cancer and chronic fatigue

April 5, 2010 | 10:36 am

Four drugs that are used to treat the AIDS virus HIV can also inhibit the replication of xenotropic murine leukemia virus-related virus (XMRV), a mouse virus that has been found in some patients with prostate tumors and chronic fatigue syndrome. Now all researchers have to do is show that XMVR is actually a cause of disease rather than a passenger virus, as most researchers now suspect.

XMRV, a retrovirus that, like HIV, inserts a DNA copy of its RNA genome into the nuclear DNA of its host, was discovered in 2006 by researchers at UC San Francisco and the Cleveland Clinic. It was first found in about a third of tumor tissues from patients with prostate cancer, particularly those with the most aggressive form of the disease. Subsequently, researchers from the Whittemore Peterson Institute for Neuro-Immune Disease in Reno said that they found it in about two-thirds of 101 patients with chronic fatigue syndrome, a mysterious debilitating illness that some doctors think is more psychological than physical. Since then, however, three further studies conducted in Europe have failed to find the virus in any patients with chronic fatigue.

Critics have roasted the European researchers -- charging bias, among other things. One potential problem, advocates of the virus theory argue, is that the European researchers did not use precisely the same assays that the Americans did. In an effort to circumvent this problem, a team led by Dr. John A. Petros, a urologist at the Emory University School of Medicine, developed a new assay for antibodies to XMRV similar to the antibody-based assays used for identifying HIV infection. They reported Monday in the journal Urology that they used the antibody test to detect XMRV in 11 of 40 patients who had undergone a radical prostatectomy, about the same proportion of patients found in other studies. Their results were confirmed by other laboratories using independent assays.

"We cannot as a scientific community begin to answer the basic questions of XMRV transmissions, frequency in the population, association with disease, etc., until we can effectively test for infection," Petros said in a statement.

If the virus can ever be shown to be a cause of prostate cancer or chronic fatigue, Dr. Ila R. Singh of the University of Utah School of Medicine, chemist Raymond F. Schinazi of the Emory University School of Medicine and their colleagues tested four HIV drugs against XMRV grown in cultures of breast cancer and prostate cancer cells. They reported Wednesday in the online journal PLoS One that the four drugs -- raltegravir, Zidovudine, tenofovir and an experimental drug called L-00870812 -- each blocked XMRV replication, but that the drugs were most effective when used in combination. "Our study showed that these drugs inhibited XMRV at lower concentrations when two of them were used together, suggesting that highly potent 'cocktail' therapies might inhibit the virus from replicating and spreading," Schinazi said in a statement.

The drugs cannot ethically be tested in prostate cancer and chronic fatigue patients, however, until it is shown that the virus actually causes disease.

-- Thomas H. Maugh II

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Comments (3)

"Now all researchers have to do is show that XMVR is actually a cause of disease rather than a passenger virus, as most researchers now suspect." I'm a scientist, and I can only speak of researchers I interact with, but everyone I know suspects that XMVR positive results could be false positives caused by contamination or antibody cross reactivity.

No known retrovirus can infect a human and live in the host for 25 years without accumulating mutations, but the reported XMVR sequences are uncannily similar to each other. That suggests contamination.

Kate Bishop and colleagues in Britain tested hundreds of patient and control samples for XMVR genomes and antibodies. They found nothing but a small number of positive antibody results, all but one in controls. Most interestingly, those positive samples were cross-reactive for unrelated viruses.

I'm not saying XMVR is a hoax. I just hope that a few well meaning scientists are not getting carried away by what they want to find.

Good, balanced article.

In a recent podcast interview (TWiV 76) with Columbia University microbiology professor Vincent Racaniello, retrovirus expert Stephen Goff, commented on the issues that have been found in both studies of CFS and prostate cancer - namely the possibility of geographic issues, strain issues, as well as the possibility that there might be PCR primers that people are using that don’t work for some strains of virus. According to Goff, one base pair is all you need in the primer to cause you to miss the virus.

Dr. Racaniello, whose blog on virology was recently honored with a Seed Media Group Research Blogging Award for the best blog of 2010 in the area of clinical research, has an excellent series of posts regarding research into XMRV as well as being a good primer for those seeking to learn more about virology. (Seed Media Group’s Research Blogging Awards recognize the outstanding bloggers who discuss peer-reviewed research at ResearchBlogging.org.)

Although the jury is still out, medical science research into viral causes for CFS, which the World Health Organization classifies as a non-psychogenic brain disease (ICD-10 G93.3), indicate that more than one virus may be causal. And although a psychosomatic hypothesis has been circulating for the past two decades, there remains no objectively proven evidence for such an assertion.

@ Edg, Goff seems unconcerned about the low mutation in XMRV, and recently pointed out that it's more like HTLV than HIV. It might simply become part of the genome and retain original infection -- replication might be restricted in some way. It's not plausible but not impossible.

If there is some type of contamination it's happening across multiple labs. At either rate, there are two new large studies on XMRV in CFS just beginning. One is being done by Ila Singh and another by glaxosmithkline, in addition to the government work.



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