Using a high-resolution cryo-electron microscopy (cryo-EM), researchers have found the immune system can prevent infection with the varicella zoster virus (VZV) by attacking an unexpected area on a key protein.

Researchers have struggled to understand exactly how herpesviruses invade cells. According to research published in Nature Communications, these viruses are enclosed in a protective membrane, and the first step in invading a cell is for the viral envelope to fuse with that membrane. In the case of VZV, the gB protein sits on the outside of the viral envelope and uses a set of molecular fingers to grab onto and fuse with cells.

This was previously known, but in an effort to improve understanding, investigators used an antibody from a patient that prevented VZV fusion with cells in cryo-EM experiments to discover where the antibody attacks gB. Surprisingly, they found that the antibody bound to a spot on gB far from the fusion fingers, suggesting that it may not need to target the fingers to prevent fusion with a cell, according to the study.

Determining exactly how the process works will take more research, and future studies could inform the design of treatments and vaccines for other herpesviruses that also rely on the gB protein, the study authors noted. 

“Vaccines are currently not available for herpesviruses, with the exception of the one that prevents VZV, so the development of vaccines that target this newly identified region of gB has the potential to solve an important medical need,” said researcher Stefan Oliver, PhD, in a statement.

Oliver added that the cryo-EM technique was essential to making the discovery.

“It was only possible to uncover this mechanism by generating one of the highest resolution structures of a viral protein-antibody pair using cryo-EM,” Oliver said. “Without the cryo-EM capabilities at SLAC these fascinating insights into the molecular mechanisms of fusion function would not have been achievable.”

REFERENCE
Cryo-EM study yields new clues to chicken pox infection [news release]. SLAC National Accelerator Laboratory; August 18, 2020. https://www6.slac.stanford.edu/news/2020-08-18-cryo-em-study-yields-new-clues-chicken-pox-infection.aspx. Accessed August 24, 2020.