The Zika virus has presented many frightening unknowns. No one knows how many people have been infected, or the long-term consequences of the epidemic. And until recently, no one knew what the Zika virus even looked like.
Researchers in Singapore have identified the structure of the Zika virus. The result reveals critical information that can aid in the development of antiretroviral treatments.
The team also reported that the Zika (ZIKV) virus is structurally similar to other epidemic flaviviruses, such as West Nile, dengue, and Japanese encephalitis viruses. However, the three-dimensional structure, visualized with 3.7Å resolution, elucidates key structural differences between Zika and other flaviviruses that make it particularly robust.
The findings were published in Nature in April 2016 and are available online.
“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 Richard Kuhn, head of Purdue’s Department of Biological Sciences. Kuhn and collaborators published similar results in Science in April 2016 as well. “Determining the structure greatly advances our understanding of Zika – a virus about which little is known.”
Zika was an underreported contagion until the 2015-2016 epidemic that affected the Americas, Pacific, and Southeast Asia. Although Zika is primarily transmitted through direct contact with the Aedes Aegypti mosquito, it can also be transmitted through semen, vaginal fluids, saliva, and urine.
Most infected with Zika are either asymptomatic or become mildly sick, but data from a 2013-2014 outbreak in French Polynesia associated Zika with an increased incidence of microcephaly in infants born to infected mothers. Researchers have also connected Zika to a severe neurological disorder called Guillain-Barre syndrome in adults. It is very rare for a virus to target the nervous system, suggesting some structural differences between ZIKV and other flaviviruses.
The scientists determined the structure of the virus using a technique called cryo-electron microscopy. In this technique, ZIKV was cryogenically frozen and imaged in an electron microscope, which uses a beam of electrons to visualize the viruses instead of light. Each image, called a micrograph, contains several, randomly oriented copies of the Zika virus. The scientists then computed tomography algorithms to generate a 3D model of ZIKV from the micrographs. The structural features of the virus were seen with 3.7Å resolution, which is sufficient to investigate the differences between ZIKV and other flaviviruses.
In some instances, ZIKV closely resembled the dengue viruses, particularly when comparing their E proteins, which are involved in receptor binding and fusion. At other sites, ZIKV more closely resembled the Japanese encephalitis and West Nile viruses.
The team also imaged West Nile (WNV) and dengue (DEN2 and DEN4 strains) viral strains to compare to ZIKV. They found that ZIKV was more thermally stable than the dengue virus. At higher temperatures (37°C and higher), ZIKV retained its infectivity, but the infectivity of both the DEN2 and DEN4 strains is greatly reduced. One domain of the E protein found in ZIKV has an extra residue insertion that is not present in the dengue viruses. This may introduce additional thermal stability.
Thermal stability may explain why the Zika virus, unlike dengue, can survive the harsh conditions of human body fluids such as urine, semen, and saliva. The structural differences between Zika and other flaviviruses could serve as points of attack for medical treatments. Currently, there is neither a vaccine nor treatment for the Zika virus.
Kostyuchenko, V.A., Lim, E. X. Y., Zhang, S. et al. (2016). Structure of the thermally stable Zika virus. Nature, ASAP.