UCLA team’s results could lead to ways to improve antiviral therapy

A new technique developed by researchers from the California NanoSystems Institute at UCLA has allowed them to become the first scientists to clearly see the intricate machinery responsible for compressing DNA into the small interior shell, or capsid, of herpes simplex virus type 1, or HSV-1, the virus responsible for causing cold sores.

3D cryo-electron microscopy reconstruction of the HSV-1 portal vertex, where DNA (red) is pumped into the viral shell.
Graphics rendering by G. Wang, Y. Ma and J. Jih

The advance could help contribute to the continued development of improved antiviral therapies — medicines used to treat not just cold sores, but also cancers and birth defects caused by other viruses in the herpesvirus family — that frequently target the viral DNA packaging process.

The team’s major accomplishment was its development and use of two techniques for image processing — symmetry relaxation and sequential localized classification — that enabled the researchers to produce highly refined 3D images of HSV-1 viral particles, or virions, seen by cryo-electron microscopy. These methods allowed the scientists to see the unique structures in HSV-1.

A paper on the work is published in the journal Nature.

“Viruses tend to be highly symmetric,” said Yun-Tao Liu, a visiting graduate student at UCLA from the University of Science and Technology of China, and the study’s co-first author. “Traditional 3D reconstruction techniques leverage this symmetry to visualize the virus, but the downside is you can’t see structures that deviate from this symmetry. To our amazement, our specialized methods enabled us to see the unique structures of the HSV-1 virion and much of the viral DNA genome.”

Read more at UCLA