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Highest resolution image of Zika virus can guide vaccine development
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Researchers have captured the highest resolution image yet of the Zika virus and said it provides a structural foundation for the design of vaccines and antiviral therapies against the virus.
“A vaccine is normally a copy of the infectious pathogen that is non-infectious but has the same shape and features of the infectious pathogen,” Michael G. Rossmann, PhD, Hanley Distinguished Professor of Biological Sciences at Purdue University, told Infectious Disease News. “It then acts on the immune system of the infectious person and produces antibodies, which neutralize the virus. So, having a knowledge of the exact shape and structure of the virus, we can now modify that structure in a sufficient way that it is non-infectious, and can be used as a vaccine.”
Rossmann and colleagues used cryo-electron microscopic single-particle reconstruction to capture the refined structure of the mature Zika virus at an unprecedented 3.1Å resolution. They achieved the improved resolution through enhanced virus preparation and data processing methods. In 2016, some of the same researchers, including Rossmann, captured a strain of Zika from the epidemic in French Polynesia at 3.8Å resolution.
This time the researchers compared the glycoprotein interactions and surface properties of Zika with the structures of other mosquito-borne flaviviruses — a group that includes dengue, Japanese encephalitis, West Nile and yellow fever — revealing that the most significant structural differences were seen at the glycosylation loop linked to receptor binding. They identified likely drug-binding pockets on the surface of the virus.
“When the virus affects the cell of a human, these are moving parts, and we can stop that movement or cause something to go wrong by carefully designing small, organic compounds which can fit into the surface of the virus, and therefore stop the motion,” Rossmann said. “It’s much like if you know how a car engine works, you can put water into the tank and stop the engine from working. It’s because you know how it works.”
Another important potential application for this structural information is combating yellow fever. Rossmann noted that yellow fever transmitted by mosquitoes delayed the building of the Panama Canal.
“A very effective vaccine has been available against yellow fever since that time, but that vaccine is now becoming not so effective, because the virus is changing all the time,” he said. “Yellow fever is very similar to Zika. It has different medical symptoms, but the virus is similar.”
Rossmann said improved knowledge of Zika — and therefore yellow fever — will be valuable in addressing an ongoing outbreak of the disease in Brazil.
“Having this knowledge of Zika virus is also very useful in designing vaccines and antiviral compounds against similar viruses,” he said. “I think this will be particularly important now, because I think the problems in Brazil are going to spread very quickly to other parts of the world.” – by Jennifer Byrne
Disclosures: The authors report no relevant financial disclosures.
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