Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015674 (chronic fatigue syndrome)
 2,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xenotropic murine leukemia virus-related virus (XMRV) is a recently discovered gammaretrovirus that has been linked to prostate cancer and chronic fatigue syndrome. This virus is therefore an important potential human pathogen and, as such, it is essential to understand its host cell tropism. Intriguingly, infectious virus has been recovered from patient-derived peripheral blood mononuclear cells. These cells express several antiviral restriction factors that are capable of inhibiting the replication of a wide range of retroviruses, including other gamma retroviruses. This raises the possibility that, similar to HIV, XMRV may have acquired resistance to restriction. We therefore investigated the susceptibility of XMRV to a panel of different restriction factors. We found that both human APOBEC3 and tetherin proteins are able to block XMRV replication. Expression of human TRIM5alpha, however, had no effect on viral infectivity. There was no evidence that XMRV expressed countermeasures to overcome restriction. In addition, the virus was inhibited by factors from nonhuman species, including mouse Apobec3, tetherin, and Fv1 proteins. These results have important implications for predicting the natural target cells for XMRV replication, for relating infection to viral pathogenicity and pathology, and for the design of model systems with which to study XMRV-related diseases.
 ...
PMID:Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors. 2019 52

Xenotropic murine leukemia virus-related virus (XMRV) is an authentic, newly recognized human retrovirus first identified in prostate cancer tissues from men with a deficiency in the innate immunity gene RNASEL. At present, studies have detected XMRV at widely different rates in prostate cancer cases (0-27%) and in patients with chronic fatigue syndrome (CFS; 0-67%). Indirect or direct modes of carcinogenesis by XMRV have been suggested depending on whether the virus was found in stroma or malignant epithelium. Viral replication in the prostate might be affected by androgens, which stimulate XMRV through a transcriptional enhancer site in viral DNA. By contrast, host restriction factors, such as APOBEC3 and tetherin, inhibit virus replication. Immune dysfunction mediated by XMRV has been suggested as a possible factor in CFS. Recent studies show that some existing antiretroviral drugs suppress XMRV infections and diagnostic assays are under development. Although other retroviruses of the same genus as XMRV (gammaretroviruses) cause cancer and neurological disease in animals, whether XMRV is a cause of either prostate cancer or CFS remains unknown. Emerging science surrounding XMRV is contributing to our knowledge of retroviral infections while focusing intense interest on two major human diseases.
 ...
PMID:The human retrovirus XMRV in prostate cancer and chronic fatigue syndrome. 2051 89

The recent discovery of xenotropic murine leukaemia virus-related virus (XMRV) in prostate cancer tissues and in the blood of individuals suffering from chronic fatigue syndrome has attracted considerable interest. However, the relevance and significance of XMRV to human disease remain unclear, since the association has not been confirmed in other studies. XMRV is the first gammaretrovirus to be found in humans. XMRV and murine leukaemia viruses share similar structures and genomic organisation. Human restriction factors such as APOBEC3 or tetherin inhibit XMRV replication. Although XMRV induces low rates of transformation in cell culture, it might be able to induce cancer by low-frequency insertional activation of oncogenes or through the generation of highly active transforming viruses. A preference for regulatory regions of transcriptional active genes has been observed after a genomic-wide analysis of XMRV integration sites. Genes related to carcinogenesis and androgen signalling have been identified in the vicinity of integration sites. The XMRV genome contains a glucocorticoid responsive element, and androgens could modulate viral replication in the prostate. Evidence supporting the involvement of XMRV in chronic fatigue syndrome is still very weak, and needs further confirmation and validation. Currently approved anti-retroviral drugs such as zidovudine, tenofovir and raltegravir are efficient inhibitors of XMRV replication in vitro. These drugs might be useful to treat XMRV infection in humans. The identification of XMRV has potentially serious health implications for the implementation of novel techniques including gene therapy or xenotransplantation, while raising concerns on the need for screening donated blood to prevent transmission through transfusion.
 ...
PMID:Evidence and controversies on the role of XMRV in prostate cancer and chronic fatigue syndrome. 2129 12