Studying this bacteriophage reveals various characteristics about viruses and their life cycle without having to study actual human viruses.
Structural biologists Juha Huiskonen and Sarah Butcher from the Academy of Finland Virus Research Centre of Excellence, University of Helsinki, have determined the structure of the double-stranded RNA virus (phi6) in co-operation with their colleagues in the European Molecular Biology Laboratory (EMBL). The virus in question is a bacteriophage, which means that instead of eukaryotic cells it infects bacteria. To the researchers' surprise, its structure turned out to be very similar to human viruses, such as rotavirus. Rotaviruses are the most common cause of severe diarrhoea, particularly in neonatal babies and young children. Diarrhoea is one of the main causes of infant mortality in developing countries.
By studying the viruses in bacteria, researchers can determine various characteristics about the life cycle of viruses that are much harder to study using dangerous human viruses. The newly described structure of the bacteriophage furthers researchers ™ understanding of how the particles of the double-stranded RNA virus are formed in the host cell. However, it is still unclear how the virus distinguishes its ™ own genetic information from that of other corresponding cellular molecules. Studying these events with the bacteriophage will help the understanding of similar events in human viruses.
The similarity of double-stranded RNA viruses that infect different organisms is probably due to their mutual, primitive origin. During evolution, the basic structure has been maintained even though the gene sequences of the viruses have changed dramatically. Corresponding similarities between different viruses have earlier been detected between a double-stranded DNA bacteriophage and an archaeal virus.
The structure of the bacteriophage was studied with electron microscopy and computational methods.
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Between the disease-discordant twins, minor yet measurable differences were detected in the expression of 1,163 transcripts, representing 827 uniquely named genes. Of this total, 3 genes were significantly over-expressed in the cells of RA patients relative to their healthy co-twins. The most significantly over-expressed gene was laeverin, a newly discovered enzyme that works to degrade proteins. The second most significantly over-expressed gene was 11 -hydroxysteroid dehydrogenase type 2 (11 -HSD2), a steroid pathway enzyme linked to inflammation and bone erosion. This gene was also found over-expressed in the synovial tissue of OA patients. The third most significantly over-expressed gene was cysteine-rich, angiogenic inducer 61 (Cyr61), well-established for its role in the formation of new blood vessels.
"Our findings provide the first evidence that laeverin is abundantly expressed in synovial tissue," notes the study's leading author, Joseph Holoshitz, M.D. "11 -HSD2 and Cyr61 have not previously been directly implicated in RA," he adds. Uncovering 3 new genes with a clear abundance in RA, this study supports the promise of microarray analysis to not only provide further insights into the genetic components of this inflammatory disease, but also to help identify candidates for therapeutic intervention.
interscience.wiley/journal/arthritis