Purdue research team determines structure of Zika virus; reveals critical insights to potential treatment


A team led by Purdue University researchers is the first to determine the structure of the Zika virus, which reveals insights critical to the development of effective antiviral treatments and vaccines.

The team also identified regions within the Zika virus structure where it differs from other flaviviruses, the family of viruses to which Zika belongs that includes dengue, West Nile, yellow fever, Japanese encephalitis and tick-borne encephalitic viruses.

Michael Rossmann (right), Purdue University’s Hanley Distinguished Professor of Biological Sciences, and Richard Kuhn, director of the Purdue Institute for Inflammation, Immunology and Infectious Diseases, stand with the cryo-electron microscope used to determine the structure of the Zika virus. (Purdue University photo/Mark Simons)
Michael Rossmann (right), Purdue University’s Hanley Distinguished Professor of Biological Sciences, and Richard Kuhn, director of the Purdue Institute for Inflammation, Immunology and Infectious Diseases, stand with the cryo-electron microscope used to determine the structure of the Zika virus. (Purdue University photo/Mark Simons)

A paper detailing the findings was published Thursday (March 31) in the journal Science and is available online.

Any regions within the virus structure unique to Zika have the potential to explain differences in how a virus is transmitted and how it manifests as a disease, said Richard Kuhn, director of the Purdue Institute for Inflammation, Immunology and Infectious Diseases (PI4D) who led the research team with Michael Rossmann, Purdue’s Hanley Distinguished Professor of Biological Sciences.

“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 Kuhn, who also is head of Purdue’s Department of Biological Sciences. “Determining the structure greatly advances our understanding of Zika – a virus about which little is known. It illuminates the most promising areas for further testing and research to combat infection.”

The Zika virus, a mosquito-borne disease, has recently been associated with a birth defect called microcephaly that causes brain damage and an abnormally small head in babies born to mothers infected during pregnancy.

It also has been associated with the autoimmune disease Guillain-Barré syndrome, which can lead to temporary paralysis. In the majority of infected individuals symptoms are mild and include fever, skin rashes and flulike illness, according to the World Health Organization.

There have been three confirmed cases of the Zika virus in Kentucky, including a pregnant woman from the Louisville area.

A representation of the surface of the Zika virus is shown. A team led by Purdue University researchers is the first to determine the structure of the Zika virus, which reveals insights critical to the development of effective antiviral treatments and vaccines. (Purdue University image/courtesy of Kuhn and Rossmann research groups)
A representation of the surface of the Zika virus is shown. A team led by Purdue University researchers is the first to determine the structure of the Zika virus, which reveals insights critical to the development of effective antiviral treatments and vaccines. (Purdue University image/courtesy of Kuhn and Rossmann research groups)

The woman had recently traveled to Central America, where the virus is known to be circulating. She and the others diagnosed in Kentucky have since recovered from the illness.

Zika virus transmission has been reported in 33 countries. Of the countries where Zika virus is circulating 12 have reported an increased incidence of Guillain-Barré syndrome, and Brazil and French Polynesia have reported an increase in microcephaly, according to WHO. In February WHO declared the Zika virus to be “a public health emergency of international concern.”

“This breakthrough illustrates not only the importance of basic research to the betterment of human health, but also its nimbleness in quickly addressing a pressing global concern,” said Purdue President Mitch Daniels. “This talented team of researchers solved a very difficult puzzle in a remarkably short period of time, and have provided those working on developing vaccines and treatments to stop this virus a map to guide their way.”

Rossmann and Kuhn collaborated with Theodore Pierson, chief of the viral pathogenesis section of the Laboratory of Viral Diseases at the National Institutes of Health National Institute of Allergy and Infectious Diseases. Additional research team members include Purdue graduate student Devika Sirohi and postdoctoral research associates Zhenguo Chen, Lei Sun and Thomas Klose.

The team’s paper marks the first published success of the new Purdue Institute for Inflammation, Immunology and Infectious Diseases in Purdue’s Discovery Park.

The university’s recently announced $250 million investment in the life sciences funded the purchase of advanced equipment that allowed the team to do in a couple of months what otherwise would have taken years, Rossmann said.

The team plans to pursue further testing to evaluate the different regions as targets for treatment and to develop potential therapeutic molecules, Kuhn said.

Kuhn and Rossmann have studied flaviviruses, the family of viruses to which Zika belongs, for more than 14 years. They were the first to map the structure of any flavivirus when they determined the dengue virus structure in 2002. In 2003 they were first to determine the structure of West Nile virus and now they are the first to do so with the Zika virus.

The National Institutes of Health National Institute of Allergy and Infectious Diseases funded the research through an existing grant to Rossmann and Kuhn together with colleagues Michael Diamond and Daved Fremont at Washington University. An emergency supplement to support Zika virus research was issued in February.

Purdue University News Service


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