Does XMRV cause human disease?
Retroviruses cause severe diseases including immunodeficiency and cancer. Recently, a novel retrovirus called Xenotropic murine leukaemia virus-related virus (XMRV) has been isolated from humans with prostate cancer and chronic fatigue syndrome. Work in my laboratory aims to investigate the link between XMRV and human diseases.
We have already established PCR-based and serological tests for XMRV in the laboratory and are currently expanding our range of assays to include ELISA for high-throughput screening and viral culture assays. These assays will be used to study the prevalence of the virus in the general population, for example UK blood donors, and in patient groups of particular interest. We will use these epidemiological patterns to help examine possible routes of transmission of XMRV.
We are also interested in the basic biology of the virus and part of the project will be to investigate the cellular tropism of infection, comparing cell-to-cell transmission with cell-free infection in a range of cell lines and primary cells under different conditions. We have shown that human restriction factors can inhibit XMRV and it has been suggested that it is also susceptible to RNase L. We will, therefore, analyse the effects of interferon treatment as well as other hormonal stimuli on XMRV infection. The mechanisms behind any enhancement or inhibition noted will be explored. We will compare XMRV replication to that of other exogenous and endogenous murine leukaemia viruses to determine general phenotypes and identify any characteristics unique to XMRV. This work will complement ongoing studies in the lab investigating the early stages of retroviral replication.
This project will provide training in a wide range of techniques including virology, molecular biology, cell biology and microscopy and will involve some work under BSL3 conditions.
Groom HC, Yap MW, Galão RP, Neil SJ, Bishop KN. (2010) Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors. Proc Natl Acad Sci U S A. 107(11):5166-71.
Groom HC, Boucherit VC, Makinson K, Randal E, Baptista S, Hagan S, Gow JW, Mattes FM, Breuer J, Kerr JR, Stoye JP, Bishop KN. (2010) Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. Retrovirology. 7:10.