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Recently, the research team of Xiao Weifu of Wuhan Virus Research Institute of the Chinese Academy of Sciences made new progress in quantitative proteomics study of Zika virus (ZIKV) infected host cells, mapping the regulation of host proteins after ZIKV infection of host cells, and systematically demonstrating the interaction between ZIKV and host proteins.
paper, Quantitative proteomic analysis, is published online in the Journal of Virology.
2015, the outbreak of the Zika virus has attracted worldwide attention, mainly through mosquitoes.
zika virus infects pregnant women, can lead to fetal glycephaly and other diseases, a serious threat to human health.
To explore host factors involved in ZIKV replication, several laboratories used gene-wide knockout techniques to screen the host factors (Nature, Cell Reports) on which ZIKV replication depends, but these studies did not shed light on how host factors changed during viral infection.
In order to systematically explore the regulation of host proteins by viral infection, Xiao's team analyzed the host cells infected with ZIKV using high-flung quantitative proteomics techniques and found 200 host proteins regulated by ZIKV infection.
further bioinsynomic analysis showed that the host proteins involved in processes such as the intraplasmic mesh unfolded protein reaction (unfold protein response), the ubigan-protease system, and the natural immune system changed significantly after ZIKV infection (Figure 1).
Subsequent functional studies have shown that the ubiquitin-protease system plays an important role in the entry process of ZIKV, that the FDA-finished drug Bortzomib for ubiquitin-protease can effectively inhibit ZIKV replication at the nM level (Figure 2), and that mouse live experiments have shown that Bortzomib can reduce the load of ZIKV in the body and relieve pathological damage caused by ZIKV.
the study was the first to map the response of host cells to ZIKV infection, to make it clear that ubiquitin protease systems play a key role in Zika virus infection, and to find that the FDA-approved drug Bortzomib is found in mosquito-sourced and human-sourced cells. Subsequent experiments in mice showed that Bortzomib was effective in suppressing virus replication at the in vivo level and alleviating pathological damage caused by the virus, providing a candidate drug for blocking the transmission of ZIKV and treating ZIKV infection.
zhang Lei an associate researcher at Wuhan Virus Institute, and Xiao Weifu, a researcher, are the first authors of the paper, and Xin Kirin, a master's student, and Zhang Bo, a researcher at Wuhan Virus Institute, and Chen Xi, Ph.D., a mass spectrometology platform at Wuhan Biotechnology Research Institute, have contributed.
the study was supported by the National Key Research and Development Program (2016YFC1200400), the Chinese Academy of Sciences Key Deployment Project (ZDRW-ZS-2016-4) and the National Natural Science Foundation (No.31500144).
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