A research team led by Purdue University structural biologist Michael Rossmann was the first to discover the structure of Zika virus — emerging mosquito-borne flavivirus closely related to dengue virus — in 2016. Using cryo-electron microscopy, the scientists created an image of the virus at a resolution of 3.8Å (Ångstrom). Now, Professor Rossmann and colleagues have scaled that number down to 3.1Å. They took advantage of Zika virus stability compared to its flavivirus cousins, allowing for a particularly accurate 3D atomic model.
“This is the most accurate picture we have of the virus so far,” Professor Rossmann said.
“With the higher resolution, it is now possible to efficiently design vaccines and engineer anti-viral compounds that inhibit the virus.”
The researchers used new virus preparation methods and updated data processing techniques to get this improved resolution.
The result of cryo-electron microscopy is an electron potential map, which can be interpreted by building an atomic model.
The best fit between the model and the map is achieved using statistical adjustments known as ‘refinement.’
“Our team extended and optimized the routine crystallographic refinement methods,” Professor Rossmann.
The team compared the new structure of Zika virus to other flaviviruses such as dengue, West Nile and Japanese encephalitis virus, which are structurally similar but cause different disease symptoms.
“We compared the surface properties of these viruses and observed differences in the landscape of the surface exposed residues,” said Dr. Madhu Sevvana, a postdoctoral researcher at Purdue University.
“We found certain structural differences on the surface, which could be a starting point for further mutational analyses.”
The team’s results were published online this week in the journal Structure.
Madhumati Sevvana et al. Refinement and Analysis of the Mature Zika Virus Cryo-EM Structure at 3.1 Å Resolution. Structure, published online June 26, 2018; doi: 10.1016/j.str.2018.05.006