[Note: The free full text pdf of this “prepublication manuscript” is available at
http://precedings.nature.com/documents/4669/version/1. "Homologous" traits are similar characteristics between organisms - in this case, a virus mimicking human protein sequence(s) & possibly causing autoimmune mitochondrial problems.]
Abstract: The 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 signaling inter alia.
Viral proteins are also homologous to members of the estrogen, 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 align 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 programs or immunosuppression may be beneficial in many of these conditions.
Source: NaturePrecedings (a Pre-Publication Research/Preliminary Findings archive), Jul 15, 2010. DOI:10.1038/npre.2010.4669.1, by Carter, CJ. Saint-Leonards on Sea, East Sussex, UK. [Email: Chris_car@yahoo.com]