Following their research on virus SIRV2, a virus found to survive in extreme environments (very hot and acidic), researchers from the University of Washington, the University of Virginia and the Institut Pasteur have discovered what appears to be a basic mechanism of resistance to heat, dehydratation and ultraviolet radiation. This finding could potentially lead to many applications, including the development of new ways to package DNA for gene therapy.
Finding effective ways of DNA packaging for its delivery is important because the human body has many ways to degrade and remove foreign DNA. Unfortunately, that protective mechanism becomes a major obstacle for doctors seeking to use genes to battle diseases. Creating an impenetrable packaging would overcome that problem, and hyperthermophilic SIRV2 seems to offer a promising template.
Extremophiles are microorganisms which thrive in extreme environmental conditions, including in extreme geothermal environments with temperatures above 80°C. In order to do so, they must have proteins and nucleic acids that are stable at extremes of temperature and pH.
The nonenveloped, rod-shaped virus SIRV2 (Sulfolobus islandicus rod-shaped virus 2) infects a microscopic organism known as Sulfolobus islandicus. This hyperthermophilic acidophile lives in extreme conditions - in nearly boiling acidic hot springs. Using cryo–electron microscopy to generate a three-dimensional reconstruction of the SIRV2 virion, scientists from the Institut Pasteur, the University of Washington and the University of Virginia discovered that, in order to survive under extreme conditions, SIRV2 forces its DNA into what is called A-form. The A-form was first identified by pioneering DNA researcher Rosalind Franklin more than a half-century ago and was commonly thought not to have biological relevance. However, thanks to this study, A-form DNA now appears to be a general mechanism in biology for protecting DNA in the most adverse conditions.
The research led by Prof. Edward Egelman (UVA) and Dr. David Prangishvili (Institut Pasteur, Department of Microbiology) finds remarkable similarities in the strategies used by the virus SIRV2 and by bacterial spores to protect their genomes under adverse environmental conditions. High resilience of spores produced by pathogenic bacteria, like Clostridium difficile, which causes colitis (inflammation of the large intestine), or anthrax-causing Bacillus anthracis, significantly hinders attempts to fight them. The study of SIRV2 may provide insight into the way bacterial spores work, and help researchers eventually to find ways to destroy them.
Finally, this research proves that, thanks to the protein of the hyperthermophilic virus SIRV2, the DNA may be organized in a way which dramatically increases its stability under the harshest conditions imaginable. As such, the viral protein could be used for designing novel DNA packages for more efficient gene therapy and development of new therapeutical solutions.
A virus that infects a hyperthermophile encapsidates A-form DNA, Science, May 22nd, 2015
Frank DiMaio1,*, Xiong Yu2,*, Elena Rensen3, Mart Krupovic3, David Prangishvili3,†, Edward H. Egelman2,†
1 Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
2 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
3 Institut Pasteur, Department of Microbiology, 25 rue du Dr. Roux, Paris 75015, France.
† Corresponding authors.
Updated on 15/06/2015