What is the Xenotropic Murine Leukemia Virus?
In 2006, a previously unknown virus was discovered during an investigation of tumour samples from prostate carcinoma sufferers geno-sections. Due to its high similarity to the already known xenotropic murine gammaretroviruses, it was named xenotropic murine leukemia virus-related virus, or XMRV for short. Other research groups reported an association between prostate cancer and XMRV based on PCR analysis results. Furthermore, a causal connection between myalgic encephalomyelitis and XMRV was proven in 2009. Mainly because of the implication of the results obtained for blood sample safety, attempts were made to reproduce the results at . However, it was found that all related findings between prostate cancer, myalgic encephalomyelitis and XMRV were due to contamination of the blood samples . For this reason, there is no firm evidence to date that there is a link between XMRV and disease , either in animals or in humans.
What is the morphology of the Xenotropic Murine Leukemia Virus?
The XMRV belongs to the Retroviridae family and is an enveloped gammaretrovirus with an RNA genome of about 8.1 kb. The virus may have arisen through a homologous recombination of two endogenous murine gammaretroviruses during the passage of a human prostate carcinoma in immunosuppressed laboratory mice. As Pre-XMRV-1 and Pre-XMRV-2, these parental viruses were named. <h3
XMRV belongs to the genus of gammaretroviruses, thus they belong to the family of retroviruses. The virus consists of a double-stranded RNA genome and reproduces itself by copying DNA. The name is derived from the close relationship to the murine leukaemia virus. The estimated length of the genome is about 8100 nucleotides and is almost 95% identical to some mouse viruses. Many of the XMRV gene sequences are almost identical to retrovirus replication. This is quite unusual, because normally this leads to a high mutation rate, as with the HI virus.
How is the Xenotropic Murine Leukemia Virus transmitted?
The XMRV has a high similarity and close relationship to many known xenotropic murine viruses. Cells from non-rodents are recognised by the virus and infected by means of receptor XPR1 (xenotropic and polytropic murine leukemia virus receptor). Scientists and physicians speculate that the virus is also sexually transmissible, but transmission from human to human has not yet been investigated, therefore it has not been conclusively proven that this transmission route is even a possibility. Cell-free as well as cellular transmission could be observed in vitro. Furthermore, it is also known that the XMRV cannot be transmitted via the air or via body fluids . In extensive tests, it could be proven that infected activated T and B cells infected other target lines in the laboratory . However, cell-free plasma could also infect other cells with XMVR . Even blood from an infected person that had been frozen for more than 25 years was still highly infectious. However, all transmission routes have not yet been sufficiently investigated and researched at this point in time to be able to prove them unequivocally.
Can the Xenotropic Murine Leukemia Virus cause disease?
Whether the XMRV can cause diseases or not seems to be an endless discussion. Associations between prostate cancer in sufferers with an RNase mutation or chronic fatigue syndrome and XMRV-positive samples have been established. However, it could be shown that laboratory contamination was the cause of these results . Two studies linked the Xenotropic Murine Leukemia Virus to prostate cancer , while other studies could not prove a connection. However, the connection between XMRV and chronic fatigue syndrome has also been refuted by numerous studies.
As a result, the journal Science published a link between XMRV and chronic fatigue syndrome, the New Zealand Blood Banks, the Canadian Department of Health and the Australian Red Cross were temporarily prompted to impose a ban on blood donations from patients with chronic fatigue syndrome. In June 2010 , the American AABB also recommended that no more blood donations be accepted from such patients.
Only very sensitive methods must be used to detect retroviruses . Therefore, on the basis of results of PCR or nested PCR tests, the suspicion has been expressed that the positive detections may have arisen due to laboratory contamination. Different studies support this thesis, because the contamination of commercial kits with mouse DNA is similar and to a large extent also has the same DNA sequence . In September 2011, the original study, which was supposed to prove that there was a link between chronic fatigue syndrome and XMRV, was withdrawn. Then in December 2011, the full publication of the study was finally retracted by Science magazine.
How is Xenotropic Murine Leukemia Virus diagnosed?
At the present time, there are no simple tests to diagnose infection with XNRV. It is essential that different tests are carried out so that the XMRV status can be determined :
- DNA test performed by PCR,
- Infectivity of the virus,
- Detection of the presence of viral proteins,
- Antibodies on the viral envelope of the Xenotropic Murine Leukemia Virus.
How could Xenotropic Murine Leukemia Virus be treated?
In 2010, a study was published in the Public Liberary of Science, which concluded that four drugs against AIDS could also suppress XMRV replication. These are two retroviral integrase inhibitors ratlegravir and L-000870812 and two nuleoside reverse transcriptase inhibitors zidovudine and tenofovir. A synergistic effect was also observed when the drugs were used together. In order to find further effective drugs against infection with the xenotropic murine leukemia virus, further research, work and studies are necessary.