Release date: 2016-08-01
The reporter learned from Tianjin University on the 28th that the research team led by Professor Yang Haitao of Tianjin University unveiled the mystery of Zika virus replication. The disclosure of this key step will help develop antiviral drugs and protect the virus on a global scale. A huge threat.
Zika virus is currently raging in South America and Latin America. In addition to causing microcephaly in newborns, viral infection can also trigger Green-Barre syndrome. The latter is a serious neurological disease that can lead to paralysis and even death. However, there are currently no drugs that can effectively control Zika virus infection.
How Zika virus replicated in host cells has been a mystery. The research article published by Yang Haitao's team in the Protein & Cell magazine unleashed the key processes and mechanisms of replication.
Almost all viruses require a protein called helicase to replicate. Zika virus helicase is a kind of "motor" protein (a kind of protein with driving ability), which converts chemical energy into mechanical energy by hydrolyzing nucleoside triphosphate, thereby realizing the melting function of double-stranded nucleic acid.
Only when the virus is melted, the single-stranded genetic material can be replicated to achieve proliferation. In this regard, the research team successfully obtained the 3D image of the Zika virus helicase function and the substrate when using X-ray single crystal diffraction technology.
Adenosine triphosphate (ATP) and metal ions are required for the helicase to perform its function. In the image, the researchers demonstrated the spatial structure of the ternary complex formed by Zika virus helicase, adenosine triphosphate, and metal-catalyzed ions at the atomic resolution level. In addition, the researchers also successfully captured the intermediate state of Zika virus helicase binding to ATP and metal ions, which is the first to reveal the flavivirus family (a mosquito-borne virus, including Zika virus, dengue virus, yellow fever virus, west Nile virus, etc.) The structure of the helicase when bound to the natural substrate ATP.
"By analyzing this structure, we can reveal how the Zika virus helicase recognizes the mechanism of ATP and metal-catalyzed ions," Yang Haitao said.
To investigate the differences in replication mechanisms between Zika virus and other flavivirus members, the researchers also analyzed the three-dimensional structure of the complex when Zika virus helicase binds to genomic RNA. They found that a passage through the helicase is responsible for "clamping" the RNA. Surprisingly, Zika virus helicase undergoes significant conformational changes upon binding to RNA, which is distinct from the helicase of the dengue virus.
Studies have shown that the flavivirus family helicase evolved a conserved molecular "motor" during evolution, which can convert chemical energy into mechanical energy by hydrolyzing nucleoside triphosphate, which is used to achieve "melting" in the process of viral replication. While using different "sports" patterns, the helicases of different viral members recognize and bind genomic RNA in different ways to meet the needs of viral replication. The interpretation of the key steps of these Zika virus replication plays a positive role in the development of antiviral drugs.
Not long ago, the research team published an article in the journal Protein & Cell to show the crystal structure of Zika virus helicase with a resolution of 1.8A. This high-resolution structure reveals a key region for the hydrolysis of nucleoside triphosphates, as well as a positive charge channel for RNA, providing an accurate model for the development of Zika virus.
Source: Xinhua News Agency
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