Abstract
AbstractThe XMRV retrovirus has been implicated in chronic fatigue syndrome and prostate cancer. A homology search comparing retroviral with human proteins revealed short contiguous amino acid strings (typically 5-8 aa) matching human proteins whose dysfunction might be expected to cause fatigue, including mitochondrial proteins related to oxidative phosphorylation, glutamate receptors and their synaptic scaffolds, muscular acetylcholine receptor scaffolds and structural proteins, components of the immune system, and phosphatidylinositol signalling inter alia. Viral proteins are also homologous to members of the oestrogen, peroxisome proliferator, and CREB activated receptor networks, all of which are implicated in prostate cancer, and to a protein, SRCAP, that controls the expression of the prostate-specific antigen. These short matches are often predicted to be antigenic, and antibodies to XMRV proteins may target their human homologues. This is supported by the presence of autoantibodies to muscarinic receptors , vimentin and LAMINB1 (all XMRV homologues) in chronic fatigue syndrome sufferers. Homologous XMRV proteins might also interfere with the protein interactomes of their human homologues. Viral mimicry of human proteins is extensive and often relevant to disease. For example Epstein-Barr viral proteins aligns with multiple sclerosis autoantigens, while HIV-1 proteins align with several components of the immune system. Mutant proteins in Huntington's disease and cystic fibrosis also align with proteins from common phages or viruses. This suggests a common theme of viral derived autoimmunity/network interference in many human disorders, which could radically change the shape of future therapy. Such viral mimicry likely relates to the idea that life evolved from viruses, leaving behind a legacy of viral derived human proteins whose homology to the current virome may be responsible for many human diseases and syndromes. Vaccination programmes or immunosuppression may be beneficial in many of these conditions.
Highlights
Chronic fatigue syndrome is an unexplained medical condition characterised by extreme mental and physical fatigue 25. and by cognitive impairment, depression and muscular pain and excessive sensitivity to light, sound and smell 41
Viral proteins are homologous to members of the oestrogen, peroxisome proliferator, and CREB activated receptor networks, all of which are implicated in prostate cancer, and to a protein, SRCAP, that controls the expression of the prostatespecific antigen
This virus expresses proteins which are homologous to several human proteins which are relevant to all of the symptoms encountered in chronic fatigue syndrome and to the proteins implicated in prostate cancer
Summary
Chronic fatigue syndrome is an unexplained medical condition characterised by extreme mental and physical fatigue 25. and by cognitive impairment, depression and muscular pain and excessive sensitivity to light, sound and smell 41. 7 Perhaps most of the population will experience this condition at some time in their lives It may be triggered by infection or trauma or by vaccination against hepatitis b 33 or against multiple infectious agents (suggested as the cause of Gulf War syndrome). Microbial infections are common in these patients 52, Perhaps the most intensively studied and hotly debated 21 viral cause of chronic fatigue syndrome is the XMRV retrovirus (Xenotropic murine leukemia virus-related virus) initially reported by Lombardi and colleagues 24. This virus has been implicated in prostate cancer 4. This virus expresses proteins which are homologous to several human proteins which are relevant to all of the symptoms encountered in chronic fatigue syndrome and to the proteins implicated in prostate cancer
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
