While viruses are commonly said to inject their DNA into cells, it isn’t always clear what “inject” means at the viral scale. Because viruses and hypodermic needles differ so much in size, who is to say whether they working according to the same physical principles? This is a question for biophysicists.
The question, it turns out, has been explored in a pair of studies led by Alex Evilevitch, Ph.D., a biophysicist affiliated with Lund University and Carnegie Mellon University. Along with his colleagues, Dr. Evilevitch has shown that viruses can convert their DNA from solid to fluid form, explaining how viruses manage to inject DNA into the cells of their victims.
One of the studies investigated the herpes virus; the other focused on bacteriophages. The results of the herpes virus investigation appeared September 7 in Nature Chemical Biology, in an article entitled, “Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection.” The results of the bacteriophage study appeared September 30 in the Proceedings of the National Academy of Sciences (PNAS), in an article entitled, “Solid-to-fluid–like DNA transition in viruses facilitates infection.”
According to Dr. Evilevitch, no one was previously aware of the phase transition from solid to fluid form in virus DNA. He noted, for example, that it was a surprise to learn that the phase transition for the herpes virus is temperature-dependent and takes place at 37°C, which is a direct adaptation to human body temperature. Dr. Evilevitch hopes that the research findings will lead to a new type of medicine that targets the phase transition for virus DNA, which could then reduce the infection capability and limit the spread of the virus.
“A drug of this type would affect the physical properties of the virus’s DNA, which means that the drug can resist the virus' mutations,” said Dr. Evilevitch.
“We found that the sliding friction between closely packaged DNA strands, caused by interstrand repulsive interactions, is reduced by the ionic environment of epithelial cells and neurons susceptible to herpes infection,” wrote the authors of the Nature Chemical Biology article. “However, variations in the ionic conditions corresponding to neuronal activity can restrict DNA mobility in the capsid, making it more solid-like.”
In the second study, which considered a bacteriophage that attacks a strain of Escherichia coli that resides in the human gastrointestinal tract, the researchers also found that virus DNA undergoes a phase transition at 37°C.
“Through a combination of single-molecule and bulk techniques, we determined how the structure and energy of the encapsidated DNA in phage λ regulates the mobility required for its ejection,” wrote the authors of the PNAS article. “Our data show that packaged λ-DNA undergoes a solid-to-fluid–like disordering transition as a function of temperature, resulting locally in less densely packed DNA, reducing DNA–DNA repulsions.”
In both studies, the authors remarked upon the physical conditions imposed by viral capsids and the dynamics of DNA injection. They described measuring the DNA pressure inside the virus that provides the driving force for infection. This pressure, which is five times higher than in an unopened champagne bottle, is generated by very tightly packed DNA inside the virus. The pressure serves as a trigger that enables the virus to eject its DNA into a cell in the host organism.