Viruses have evolved a number of defense mechanisms that make it difficult for medication to attack them. Typically, antivirals target surface protein receptors, which the viruses eventually develop a resistance to, rendering the treatment ineffective. Alex Evilevitch of Carnegie Mellon University recently led two studies that showed how some viruses are able to undergo a phase change and temporarily turn their DNA from a solid to a liquid in order to facilitate infection. This could lead to a new treatment option that targets the viral DNA when it is most vulnerable. The papers were published in Nature Chemical Biology and Proceedings of the National Academy of Sciences.
Viruses can have either DNA or RNA. Viral DNA is typically bound very tightly within the shell-like structure called a capsid, existing in a frozen crystalline structure under tremendous pressure. In order for the genetic material to rapidly shoot out and infect host cells, it must escape through an opening in the capsid that is too small for the crystalline DNA to escape. Evilevitch sought to find out how this could be possible. It turns out the answer is that the DNA undergoes a phase change, temporarily becoming liquid and allowing the DNA to rapidly squirt out to cause infection.
Image credit: Carnegie Mellon University
"The exciting part of this is that the physical properties of packaged DNA play a very important role in the spread of a viral infection, and those properties are universal," Evilevitch said in a press release. "This could lead to a therapy that isn't linked to the virus' gene sequence or protein structure, which would make developing resistance to the therapy highly unlikely."
The paper in Nature Chemical Biology is based on study of Herpes Simplex virus type 1 (HSV-1), which causes infectious disease in humans. The PNAS paper looked at bacteriophage lambda, that infects E. coli. The viruses were both subjected to small angle x-ray scattering (SAXS) and high-powered microscopy to obtain information about the shape of the DNA’s arrangement and how compressed it is within the capsid.
Evilevitch’s team discovered that when the virus reaches 37 degrees Celsius—the average temperature of the human body—the crystalline structure of the DNA begins to melt into a liquid. The rising temperatures increases the internal pressure of the capsid, allowing the DNA to stream out at a rate of about 60,000 base pairs per second. This temperature-dependent system prevents premature ejection of the virus’s genetic material, ensuring it won’t waste it when conditions are not ideal.
[Hat tip: i09]
