A analysis crew led by scientists at the University of California, Riverside, has outlined how the Zika virus, which constituted an epidemic menace in 2016, suppresses the immune system of its host.
The Zika virus, or ZIKV, spreads by way of mosquito bites and sexual activity. Currently, no accredited vaccine or antivirals in opposition to ZIKV exist.
“Suppressing host immunity is a common strategy employed by viruses to achieve successful infection,” mentioned Jikui Song, a professor of biochemistry at UCR, who co-led the research. “Our work provides valuable structural and functional information on the interaction between ZIKV and its host and offers a framework for the development of vaccines and antivirals.”
The research seems in Nature Structural & Molecular Biology.
Song defined the steps concerned in suppressing the host immune response. ZIKV encounters the first line of protection by means of a sort I interferon, or IFN, response in the host. Secreted by contaminated cells, IFNs are pure substances that assist the host’s immune system battle an infection. Once ZIKV infects the cell, it presents a nonstructural protein, NS5, which interacts with a key participant in the sort I IFN pathway: the STAT2 protein. The interplay between ZIKV NS5 and STAT2 degrades STAT2, which inhibits the sort I IFN response.
The analysis concerned first fixing the crystal construction of a posh between a big fragment of ZIKV NS5 and STAT2. This crystal structure guided the researchers in fixing the cryo-EM construction of ZIKV NS5 and STAT2, which then led them to provide you with a mannequin for how ZIKV NS5 suppresses human STAT2.
“Understanding the interaction, at the molecular level, between ZIKV NS5 and the host immune factor STAT2, opens up a new window for the rational design of live attenuated vaccines and antivirals” mentioned research co-leader Rong Hai, an assistant professor of virology at UCR. “Targeting the virus-host interaction may also provide an important approach for drug development against SARS-CoV-2, the virus that causes COVID-19.”
The researchers additionally generated a panel of mutant ZIKV viruses.
“To our knowledge, these are the first NS5-based ZIKV mutants, which have the potential to be used as live attenuated ZIKV vaccines,” Hai mentioned.
Next, the researchers will work on the construction and performance of SARS-CoV-2 proteins to determine new targets in opposition to COVID-19.
Boxiao Wang et al, Structural foundation for STAT2 suppression by flavivirus NS5, Nature Structural & Molecular Biology (2020). DOI: 10.1038/s41594-020-0472-y
University of California – Riverside
Study provides insights into how Zika virus suppresses the host immune system (2020, August 12)
retrieved 12 August 2020
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