The structure of the Zika virus has been revealed for the first time – opening the way to the development of new treatments and vaccines to counter the mosquito-borne disease.
Researchers, led by Purdue University, Indiana, USA, have also identified regions within the Zika virus structure that differ from other flaviviruses, the family of viruses to which Zika belongs, detailing their findings in the latest edition of Science.
Professor Richard Kuhn, director of the Purdue Institute for Inflammation, Immunology and Infectious Diseases (PI4D), who was co-lead researcher, said the identification of any unique Zika structures could help to explain the differences in how a virus is transmitted and how it manifests as a disease.
“The structure of the virus provides a map that shows potential regions of the virus that could be targeted by a therapeutic treatment, used to create an effective vaccine or to improve our ability to diagnose and distinguish Zika infection from that of other related viruses,” said Prof Kuhn.
“Determining the structure greatly advances our understanding of Zika. It illuminates the most promising areas for further testing and research to combat infection."
The Zika virus, which was declared a public health emergency of international concern by the World Health Organisation (WHO) in February, has most recently been associated with microcephaly<!, which causes brain damage and an abnormally small head in babies born to mothers infected during pregnancy>.
It also has been associated with Guillain-Barré syndrome, an autoimmune disease that can lead to temporary paralysis.
Professor Michael Rossmann, who worked alongside Professor Kuhnsaid, said: “We were able to determine through cryo-electron microscopy the virus structure at a resolution that previously would only have been possible through X-ray crystallography.
“Since the 1950s X-ray crystallography has been the standard method for determining the structure of viruses, but it requires a relatively large amount of virus, which isn’t always available; it can be very difficult to do, especially for viruses like Zika that have a lipid membrane and don’t organise accurately in a crystal; and it takes a long time.
“Now we can do it through electron microscopy and view the virus in a more native state. This was unthinkable only a few years ago.”
The team studied a strain of Zika virus isolated from a patient infected during the French Polynesia epidemic and determined the structure to 3.8Å – a near-atomic resolution – finding that the structure is very similar to other flaviviruses, with an RNA genome surrounded by a lipid membrane inside an icosahedral protein shell.
All known flavivirus structures differ in the amino acids that surround a glycosylation site in the virus shell. The glycosylation site in the Zika, however, protrudes from the surface of the virus and a carbohydrate molecule of sugars is attached to the viral protein surface at this site.
The glycosylation site and surrounding residues on Zika virus may also be involved in attachment to human cells, and the differences in the amino acids between different flaviviruses could signify differences in the kinds of molecules to which the virus can attach and the different human cells it can infect, Professor Rossmann said.
“If this site functions as it does in dengue and is involved in attachment to human cells, it could be a good spot to target an antiviral compound,” he said.
“If this is the case, perhaps an inhibitor could be designed to block this function and keep the virus from attaching to and infecting human cells.”
Further testing is to be undertaken to evaluate the different regions as targets for treatment and to develop potential therapeutic molecules.
Science 31 March 2016; doi: 10.1126/science.aaf5316 (2016)
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