As a consequence of this award, Professor Alex Evilevitch, from the Carnegie Mellon University, will conduct an investigation, featuring an array of experimental tools, of how the physico-chemical properties of double-stranded DNA viruses relate to viral assembly and infectivity. The work has the potential to impact broadly the field of virology, and could inform new thinking about viral diseases. This project is funded jointly by the Chemistry of Life Processes Program in the Division of Chemistry and the Genetic Mechanisms Cluster of the Molecular and Cellular Biosciences Division of the Directorate for Biological Sciences.
Viruses consist of a protein shell called a capsid that protects the viral genome. Often, and especially in double-stranded DNA viruses, the negatively charged genome is strongly confined within the small capsid volume, leading to tens of atmospheres of genome pressure. Dr. Evilevitch and his co-workers have demonstrated that this internal pressure is responsible for DNA release into the cell and subsequent infection. Because all viral capsids are permeable to water and ions, the distribution and chemical potential of water molecules inside the capsid determine the energy state of the encapsidated DNA. At small DNA-DNA separations inside viral capsids (20-30 Angstroms), the electrostatic forces are dominated by the DNA hydration force, the force required to remove one water molecule from the DNA surface to the bulk solution. Dr. Evilevitch aims to demonstrate that the DNA hydration force is a key physical parameter responsible for successful delivery of the viral genome into the host cell. The energy of encapsidated viral genomes will be measured with micro-calorimetry, and DNA hydration forces will be studied with atomic force microscopy. Because the hydration force is dependent on the DNA packaging density, strong correlations are likely to exist between the physical evolution of the dimensions of viruses and the genetic evolution of viruses. Insight into this physical aspect of viral evolution will be provided by this work.
Dr. Evilevitch's work will enhance fundamental understanding of how viruses function. Most current anti-viral treatments slow down but fail to cure viral infection fully. Rapid mutations of viral components help virions to escape interaction with highly specific drug molecules. Knowledge of the principles underlying viral assembly, infectivity and virion survival is highly relevant to the mission of finding the remedy to many infectious diseases. Learning how to control the viral genome hydration force can lead to a new approach for interference with viral infections.
The educational impact of this work will stem from training of graduate students and enhancement of the undergraduate science curriculum, with the creation of interdisciplinary and inter-departmental undergraduate courses in physical virology, microbiology and biophysics.
