An artistic rendering of the Zika virus structure.
Credit: Dr Guntur Fibriansah / Duke-NUS Medical School
An important breakthrough in understanding the Zika virus structure and
its behaviour has been highlighted in a study by Duke-NUS Medical School
(Duke-NUS) scientists.
Published online on 19 April 2016 in the journal Nature,
their findings reveal the Zika virus structure and identify potential
sites on the virus to target with therapeutics. This knowledge will help
worldwide efforts to fight the poorly understood virus, which is a
currently a public health and research priority.
Associate Professor Shee-Mei Lok and her team from Duke-NUS imaged the
Zika virus under a cryo-electron microscope from a large number of
purified viral particles. By using thousands of images, they
reconstructed a high-resolution cryo-electron microscopy structure of
the Zika virus.
The high-resolution structure of the Zika virus showed that the overall
virus architecture is similar to other flaviviruses such as the West
Nile and dengue viruses. However, the team found that the Zika virus is
more thermally stable than the dengue virus, and is also structurally
stable even when incubated at 40 degrees Celsius, mimicking the body
temperature of extremely feverish patients after virus infection.
The structure also revealed that the Zika virus surface proteins have
tighter interactions compared to the dengue virus, therefore making it
more stable than the dengue virus. This may explain its ability to
survive in harsh conditions such as semen, saliva and urine. In addition
to transmission by the bite of an infected mosquito, the structural
stability of the virus makes it more resilient, which likely explains
its special ability to transmit through sexual contact. Similar viruses,
such as dengue and West Nile, do not spread through sexual contact.
Overall, the findings suggest that antibodies or drugs that destabilise
the structure of the Zika virus may help to reduce the severity of the
disease or limit the spread of the virus.
"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 Assoc Prof Lok from the Emerging
Infectious Diseases Programme at Duke-NUS.
"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."
Assoc Prof Lok's next step is to understand the effect of potent
antibodies on the Zika virus. By examining the structure presented in
this study, her team will work to determine how the antibodies could be
used to kill the virus. They also hope to identify which potent
antibodies could be used to treat people in emergency situations, such
as a sudden outbreak or in the case of infection during pregnancy.
The authors include Dr Victor Kostyuchenko, Elisa Lim and Dr Shuijun Zhang from Duke-NUS.
The Zika virus, a mosquito-borne virus, is mainly transmitted to people
through the bite of infected Aedes mosquitoes. It causes Zika virus
disease which presents symptoms such as mild fever, skin rashes,
conjunctivitis, muscle and joint pain, malaise or headache in infected
people.
In February 2016, the Zika virus was declared by the World Health
Organization (WHO) to be a public health emergency of international
concern. (1) This was a result of worldwide outbreaks of the virus
starting in 2013 which have been associated with neurological disorders
such as microcephaly in foetuses and Guillian-Barré syndrome in adults.
(2)
###
(1) WHO statement on the first meeting of the International Health
Regulations (2005) (IHR 2005) Emergency Committee on Zika virus and
observed increase in neurological disorders and neonatal malformations.
(2016, February 1). Retrieved April 13, 2016, fromhttp://www.who.int/mediacentre/news/statements/2016/1st-emergency-committee-zika/en/
(2) Zika virus. (n.d.). Retrieved April 13, 2016, fromhttp://www.who.int/mediacentre/factsheets/zika/en/
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