Prions and retroviruses -- an unholy alliance?

September 07, 2007

In the Institute of Molecular Virology of the GSF - National Research Center for Environment and Health in Neuherberg/Munich (Helmholtz Association of German Research Centres) the group is continuing to search for cellular components whose make-up is changed as a result of a prion infection. In collaboration with colleagues from the Technical University of Munich and the University of Heidelberg, the group used micro-array technologies - micro-arrays are chips with thousands or tens of thousands of DNA or protein probes - and could demonstrate that the expression of endogenous retroviruses is influenced by infectious prion proteins in tests with mouse cells.

Prions - an abbreviation for proteinaceous infectious particles - work as a trigger to a set of diseases of the brain and nervous system, the so-called spongiform encephalopathies. These include BSE in cattle, scrapie in sheep and Creutzfeldt Jakob's Disease in humans. Prions are structural variants of a normal protein found in healthy tissues - especially in the brain. The devastating effect of infectious prions is that, once they have entered the organism, they can modify the normal "healthy" prion proteins to create more infectious prions, and thus cause the illness to progress. However, as yet, little is known about the molecular mechanisms of pathogenesis, the role of co-factors and the interaction of prion proteins with cellular components.

Retroviruses insert their genetic information into the genome of host cells. In the case of endogenous retroviruses, this involves retroviral infections from long ago, which were transmitted through many generations by means of the germ line. Nearly ten percent of the genome of mice and humans consists of endogenous retroviral sequences that have accumulated during the course of evolution. Indeed, most structural genes of endogenous retroviruses are inactive, but many regulatory elements, such as binding sites for transcription factors, often remain active and can influence neighbouring cellular genes.

The GSF scientists infected mouse neural cells kept in culture with infectious prion proteins and subsequently analysed the expression patterns of endogenous retroviruses. The results showed that the expression of a set of endogenous retroviral sequences is influenced by the prion infection: in comparison with uninfected cells, the expression partly increased but also partly decreased - depending on the cell line and the type of endogenous retroviruses. These effects could be suppressed by pentosan-polysulphate, an anti-prion drug, which means that the influence of the expression can be attributed to the prions and not to some secondary effects.

These observations suggest that prion proteins may stimulate the production of retroviral particles by activation of endogenous retroviruses. Subsequently, these retrovirus-like particles could transport prion proteins from cell to cell, and thus spread the infection.

These studies were carried out within the scope of the "Bavarian Research Cooperation Prions" (FORPRION) in the Association of Bavarian Research Cooperations. FORPRION was founded in 2001 following the appearance of the first BSE cases in Bavaria and was financed equally from the budgets of the Bavarian State Ministry for Science, Research and Art, and the Bavarian State Ministry of Health Food and Consumer Affairs.

Through basic and applied research the consortium aims to make progress in the diagnosis and therapy of human and animal prion diseases, as well as in the field of preventive consumer protection. FORPRION linked up 25 projects, based at five Bavarian universities and in institutes of the Max Planck Society. The financial support of the Bavarian Research Cooperation Prions FORPRION ended in June, 2007.
-end-
Literature:
A. Stengel, C. Bach, I. Vorberg, O. Frank, S. Gilch, G. Lutzny, W. Seifarth, V. Erfle, E. Maas, H. Schätzl, C. Leib-Mösch, A. D. Greenwood: Prion infection influences murine endogenous in neuronal cells. Biochemical and Biophysical Research Communications 343 (2006) 825-831

Helmholtz Zentrum München - German Research Center for Environmental Health

Related Genome Articles from Brightsurf:

Genome evolution goes digital
Dr. Alan Herbert from InsideOutBio describes ground-breaking research in a paper published online by Royal Society Open Science.

Breakthrough in genome visualization
Kadir Dede and Dr. Enno Ohlebusch at Ulm University in Germany have devised a method for constructing pan-genome subgraphs at different granularities without having to wait hours and days on end for the software to process the entire genome.

Sturgeon genome sequenced
Sturgeons lived on earth already 300 million years ago and yet their external appearance seems to have undergone very little change.

A sea monster's genome
The giant squid is an elusive giant, but its secrets are about to be revealed.

Deciphering the walnut genome
New research could provide a major boost to the state's growing $1.6 billion walnut industry by making it easier to breed walnut trees better equipped to combat the soil-borne pathogens that now plague many of California's 4,800 growers.

Illuminating the genome
Development of a new molecular visualisation method, RNA-guided endonuclease -- in situ labelling (RGEN-ISL) for the CRISPR/Cas9-mediated labelling of genomic sequences in nuclei and chromosomes.

A genome under influence
References form the basis of our comprehension of the world: they enable us to measure the height of our children or the efficiency of a drug.

How a virus destabilizes the genome
New insights into how Kaposi's sarcoma-associated herpesvirus (KSHV) induces genome instability and promotes cell proliferation could lead to the development of novel antiviral therapies for KSHV-associated cancers, according to a study published Sept.

Better genome editing
Reich Group researchers develop a more efficient and precise method of in-cell genome editing.

Unlocking the genome
A team led by Prof. Stein Aerts (VIB-KU Leuven) uncovers how access to relevant DNA regions is orchestrated in epithelial cells.

Read More: Genome News and Genome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.