High Resolution Structure of Zika virus Expected to Aid Vaccine Development

A team of molecular virologists used advanced cryo-electron microscopy techniques to establish a high-resolution structure for the Zika virus, a formerly neglected pathogen that has recently been associated with microcephaly in fetuses and with Guillian–Barré syndrome in adults.

Researchers have historically relied on NMR and X-ray diffraction techniques to determine the structures of molecular complexes and proteins that play a role in the causes of various disease states. Structural information about a variety of medically important proteins and drugs has been obtained by these methods. Cryo-EM is a complementary analytical technique that provides near-atomic resolution without requirements for crystallization or limits on molecular size and complexity imposed by the other techniques. Cryo-EM allows the observation of specimens that have not been stained or fixed in any way, showing them in their native environment while integrating multiple images to form a three-dimensional model of the sample.

Investigators at Duke–National University (Singapore) described the .37 nm resolution cryo-electron microscopy structure of Zika virus in the April 19, 2016, online edition of the journal Nature. They reported that the overall architecture of the virus was similar to that of other flaviviruses such as the West Nile and dengue viruses. However, the cryo-electron microscopy structure showed a virus with a more compact surface. In addition, Zika virus was more thermally stable than the Dengue virus, and was also structurally stable even when incubated at 40 °C. This structural stability of the virus helps to explain how it is able to survive in the harsh conditions of semen, saliva, and urine.

"This is exciting, as our structure will provide important clues to other researchers around the world who are working to find therapeutic agents against the Zika virus," said senior author Dr. Shee-Mei Lok, assistant professor in the emerging infectious diseases program at Duke–National University. "Additionally, we have shown that the Zika virus contains structures that are unique from the viruses in the same family that affect brains, such as the West Nile virus, and also those that cause fever, such as the Dengue virus. These structures can be mutated to better understand how they influence the Zika virus infection in humans and can also potentially lead to the development of a safe vaccine that has reduced side effects."

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Duke–National University