Bringing Structure to Biology
Structure of Zika Virus Revealed
The Zika virus has been linked to microcephaly and other neurological damage in foetuses. The virus is spreading so rapidly that the World Health Organization recently declared it to be an emergency of international concern. Scientists worldwide are working to study the virus, its health impacts and possible therapies, cures or vaccines.
On 31 March 2016, an exciting breakthrough was announced by the groups of Michael G. Rossmann and Richard Kuhn at Purdue University, in collaboration with Theodore Pierson at NIH. The 3D structure of the virus was determined in near-atomic detail, by cryo-electron microscopy (EM). The structure is described in the journal Science, in a paper entitled “The 3.8Å resolution Cryo-EM structure of Zika Virus”.
When asked what was critical in solving the 3D structure, Professor Rossmann comments: "The structure determination was possible because Purdue University gave us funds to purchase a direct-electron detector for our existing FEI Titan Krios electron microscope. Given these tools and, most importantly, the ability to produce undamaged Zika particles, there were no unusual problems encountered in determining the structure." On the role of public archives in rapidly disseminating results of cutting-edge research he notes: "As you know, with public archives such as PDB and EMDB the structure is immediately and freely available to all researchers and medical scientists in the world."
Professor Michael Rossmann of Purdue University, one of the scientists responsible for the 3D structure determination of the Zika virus, pictured here during a visit to EMBL-EBI a few years ago.
Zika virus is related to other mosquito-borne viruses that are responsible for dengue, yellow fever and West Nile fever. This group, called the Flaviviridae, have an RNA genome and live in a mosquito before infecting humans. The Zika fever results in a rash covering the body, fever, joint pain and a general feeling of discomfort. While the symptoms in adults are not generally severe or life threatening, in pregnant women the infection has been linked to brain defects in their unborn babies. So far however, doctors and scientists have been unable to prove that the viral infection in mothers is the direct cause of the birth defects. More research is urgently required to further understand the virus and to develop therapeutics and a vaccine. The newly-solved structure indicates that Zika differs from Dengue virus, especially in the regions where carbohydrates are attached to the virus surface. These regions and the carbohydrates might affect how the virus infects human cells, and the authors hypothesise that the carbohydrates may function as attachment sites of the virus to host cells.
3D model and EM map of the Zika virus. The model is coloured with protein components shown in blue, cream and green. The carbohydrates decorating the surface, which might be involved in attaching the virus to a host cell, are shown in red. The inset shows a projection of the EM map, revealing its 5-fold symmetry.
The 3D structure of the Zika virus is now freely and publicly available to researchers through the Protein Data Bank (PDB; atomic coordinates) and the Electron Microscopy Data Bank (EMDB; EM map). The structural information will facilitate accelerated development of new antiviral drugs and vaccines.