June 30, 2011 Researchers have identified an altered expression of endogenous retroviruses in BSE-infected macaques. Prion diseases such as Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy (BSE) in cattle are transmissible neurodegenerative diseases linked to the aggregation of the prion protein in the central nervous system. It is known that the aggregation of prion proteins promotes neuronal decay with fatal consequences for the infected individual. However, there is only a limited understanding of how neurons are lost and which molecules are involved.
Researchers at the Leibniz Institutes for Zoo and Wildlife Research (Berlin) and for Primate Research (Göttingen) together with colleagues from the Helmholtz Center Munich have now found that the expression of so-called endogenous retroviruses is altered upon BSE-infection. Their study, for which they used BSE infected non-human primates, could guide new treatment strategies for human Creutzfeldt-Jakob disease.
Endogenous retroviruses are viruses that after infection have been incorporated into the germline DNA (in eggs or sperm) of an organism. In this state, they are transmitted from one generation to the next. These retroviral elements, which can represent up to ten per cent of the genome, were often regarded as dead freight that has been accumulated over millions of years. However, recent work indicated that endogenous retroviruses can be re-activated under certain circumstances.
Now researchers from two cooperating Leibniz Institutes and the Helmholtz Center Munich investigated the expression of endogenous retroviruses in BSE-infected long-tailed macaques as a model for human Creutzfeldt-Jakob disease. When brain samples from diseased macaques, i.e. macaques that are infected with prions, were compared to healthy controls, they found that endogenous retroviruses belonging to the class of gamma retroviruses were more highly expressed. Previous research showed that exogenous gamma retroviruses can induce fatal spongiform encephalopathies without prion aggregates being present in mice, perhaps a similar effect to that observed in the macaques. "Therefore, we speculate that the observed up-regulation of the endogenous gamma retroviruses may induce or exacerbate the pathological consequences of BSE-associated neurodegeneration," says Alex Greenwood, a lead author of the study.
Furthermore, the research group observed a decreased expression of a class 2 endogenous retrovirus in the brain of BSE-infected macaques. Previous findings have shown that these viral particles can be produced and released by living cells. "Here, for the first time we see evidence of an expressed retroviral capsid protein that is encoded by an endogenous retrovirus in a non-human primate brain," says Dirk Motzkus, corresponding author of the study. The scientists also showed that the retrovirus is down-regulated upon BSE-infection.
"As retroviral infections can be treatable, this may suggest completely new future treatment strategies for Creutzfeldt-Jakob patients," says Dirk Motzkus.
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- Alex D Greenwood, Michelle Vincendeau, Ann-Christin Schmadicke, Judith Montag, Wolfgang Seifarth, Dirk Motzkus. Bovine spongiform encephalopathy infection alters endogenous retrovirus expression in distinct brain regions of cynomolgus macaques (Macaca fascicularis). Molecular Neurodegeneration, 2011; 6 (1): 44 DOI: 10.1186/1750-1326-6-44
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