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Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
Published on: August 23, 2016
Structure of the thermally stable Zika virus
Victor A Kostyuchenko1,2, Elisa X Y Lim1,2, Shuijun Zhang1,2
1Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.
Abstract:
Zika virus (ZIKV), formerly a neglected pathogen, has recently been associated with microcephaly in fetuses, and with Guillian-Barré syndrome in adults. Here we present the 3.7 Å resolution cryo-electron microscopy structure of ZIKV, and show that the overall architecture of the virus is similar to that of other flaviviruses. Sequence and structural comparisons of the ZIKV envelope (E) protein with other flaviviruses show that parts of the E protein closely resemble the neurovirulent West Nile and Japanese encephalitis viruses, while others are similar to dengue virus (DENV). However, the contribution of the E protein to flavivirus pathobiology is currently not understood. The virus particle was observed to be structurally stable even when incubated at 40 °C, in sharp contrast to the less thermally stable DENV. This is also reflected in the infectivity of ZIKV compared to DENV serotypes 2 and 4 (DENV2 and DENV4) at different temperatures. The cryo-electron microscopy structure shows a virus with a more compact surface. This structural stability of the virus may help it to survive in the harsh conditions of semen, saliva and urine. Antibodies or drugs that destabilize the structure may help to reduce the disease outcome or limit the spread of the virus.
Insights
The Zika virus (ZIKV) structure is similar to other flaviviruses but more compact and thermally stable. This stability may explain its survival in bodily fluids and suggests new therapeutic targets.
Area of Science:
- Structural biology
- Virology
- Microbiology
Background:
- Zika virus (ZIKV) is a pathogen linked to severe health issues like fetal microcephaly and Guillain-Barré syndrome.
- Understanding ZIKV's structure is crucial for developing effective antiviral strategies.
- Previous flavivirus research provides a comparative framework for ZIKV structural analysis.
Purpose of the Study:
- To determine the high-resolution cryo-electron microscopy structure of the Zika virus.
- To compare the ZIKV structure, particularly the envelope (E) protein, with other flaviviruses.
- To investigate the structural stability of ZIKV and its implications for infectivity and transmission.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to resolve the ZIKV structure at 3.7 Å resolution.
- Sequence and structural comparisons were performed between the ZIKV E protein and those of other flaviviruses (e.g., West Nile, Japanese encephalitis, Dengue).
- Thermal stability assays and infectivity studies at varying temperatures were conducted.
Main Results:
- The overall architecture of ZIKV is similar to other flaviviruses, but its structure is more compact.
- Specific regions of the ZIKV envelope (E) protein show similarities to neurovirulent flaviviruses and Dengue virus (DENV).
- ZIKV particles exhibit significant structural stability at 40°C, unlike less stable DENV serotypes, correlating with its infectivity.
Conclusions:
- The structural stability of ZIKV may contribute to its survival in challenging environments like semen, saliva, and urine.
- Targeting the ZIKV structure with antibodies or drugs that induce destabilization could be a viable therapeutic approach.
- Further research into the E protein's role in flavivirus pathogenesis is warranted.
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