CEM Reveals Common Herpes Virus Structure

Researchers at the MRC-University of Glasgow Centre for Virus Research have used Nobel Prize- winning cryo-electron microscopy to obtain high resolution images of the biological mechanisms used by the common herpes virus to infect people. The researchers hope that these findings could lead to the development of new drugs to treat illnesses caused by the virus which include both cold-sores and chicken pox. Members of this family of viruses can also cause cancers and severe illnesses in unborn children.

However, at only 1/10,000th of a millimetre in diameter, the protective capsid, (shell) where the herpes virus stores DNA which will be used to infect its host, has until now been difficult for scientists to analyse.

Cryo-electron microscopy enabled the scientists to reveal the structure of a motor-like assembly called a portal. Herpes viruses pump their DNA into preassembled capsids through the portal. When a herpes virus infects our cells, the DNA is ejected from the capsid by the same portal machinery.

Study lead author Dr David Bhella, from the MRC-University of Glasgow Centre for Virus Research, said: “Cryo-electron microscopy, combined with new computational image processing methods allowed us to reveal the detailed structure of the unique machinery by which the virus packs DNA into the capsid. The DNA is packed very tightly, reaching a pressure similar to that inside a bottle of Champagne.”

Dr Richard Henderson at the MRC Laboratory of Molecular Biology was awarded the 2017 Nobel Prize in Chemistry alongside Professor Jacques Dubochet and Dr Joachim Frank for developing cryo-EM for the high-resolution structure determination of biomolecules in solution.

Dr Jonathan Pearce, Head of Infections and Immunity at the MRC, said: “Dr Bhella and his team have now used this technique to elucidate the structure of the herpes virus, revealing a ‘molecular machine’ that is involved in virus replication. The findings provide scientists with a better understanding of the virus and its anatomy, and, in turn, an insight into potential new therapeutic targets.

“These elegant experiments exemplify the potential of the Scottish Centre for Macromolecular Imaging due to be launched later this year at the CVR, which will support vital research into diseases posing the greatest threat to human health.”

The study, ‘Structure of the herpes-simplex virus portal-vertex’ is published in PLOS Biology. The work was funded by the MRC.