Cells and DNA Double Helix
Medical Research

How Viruses Reproduce: A Better Understanding

Researchers are drawing closer to discovering exactly what drives DNA into a virus during replication – and a better understanding of that viral reproduction could help fight infectious pathogens.

Researchers the the Perelman School of Medicine at the University of Pennsylvania, the Georgia Institute of Technology, and Columbia University, reported their finding in The Journal of Physical Chemistry B.

The team reported that DNA may go through a repetitive cycle of contraction and elongation, or as they put it, “scrunching,” to generate the forces required to drive the DNA into a virus during replication.

During replication, viruses take over the host cell machinery to make copies of their genetic material and build protein shells called capsids to contain their genomic DNA or RNA. In some DNA viruses, such as herpes viruses, the empty capsid forms first, and the DNA is then packaged by a protein “motor” on the capsid.

In 2015, team leader Stephen C. Harvey, PhD, an adjunct professor in the department of Biochemistry and Biophysics at Penn, Harvey proposed that the traditional model in which the proteins push the DNA forward with a series of lever-like motions might be wrong. He suggested that the proteins might generate a cycle of DNA dehydration and rehydration. DNA is known to shorten by about 25 percent when it is dehydrated. He proposed that the resulting cycle of shortening and lengthening motions could be coupled to a DNA-protein grip-release cycle to generate forward motion. He called this the “scrunchworm model.”

“For some time now, we have been contemplating how viral DNA gets into the capsid so that one day we can block this step as a way to halt infection,” Harvey said. They tested the scrunchworm model in a series of computer simulations. The structures of the herpes viruses are not known with sufficient resolution to permit this kind of modeling, so the team examined DNA packaging in phi29, a DNA virus of similar structure that infects bacteria. They examined the interaction of DNA with the phi29 connector proteins, which form half of the protein motor. The DNA spontaneously underwent scrunching motions, without being pushed or pulled by protein levers.

This provides the first support for the scrunchworm model.

It is essential to test the scrunchworm model experimentally, and Harvey has formed a collaboration with two other research groups to test predictions made by the scrunchworm model. “Even if these experiments disprove the scrunchworm model, they will provide information that will help us figure out how these motors work,” Harvey said. “The purpose of modeling is to drive experiments and simulations that advance our understanding, regardless how they turn out.”

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