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Ubiquitin-Modified Proteome of SARS-CoV-2-Infected Host Cells Reveals Insights into Virus-Host Interaction and
Huan Zhang1, Huanying Zheng2, Jinying Zhu1
1Key Laboratory of Zoonotic of Liaoning Province, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, Liaoning Province, P. R. China.
Abstract:
The outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a serious threat to global public health. The mechanism of pathogenesis and the host immune response to SARS-CoV-2 infection are largely unknown. In the present study, we applied a quantitative proteomic technology to identify and quantify the ubiquitination changes that occur in both the virus and the Vero E6 cells during SARS-CoV-2 infection. By applying label-free, quantitative liquid chromatography with tandem mass spectrometry proteomics, 8943 lysine ubiquitination sites on 3086 proteins were identified, of which 138 sites on 104 proteins were quantified as significantly upregulated, while 828 sites on 447 proteins were downregulated at 72 h post-infection. Bioinformatics analysis suggested that SARS-CoV-2 infection might modulate host immune responses through the ubiquitination of important proteins, including USP5, IQGAP1, TRIM28, and Hsp90. Ubiquitination modification was also observed on 11 SAR-CoV-2 proteins, including proteins involved in virus replication and inhibition of the host innate immune response. Our study provides new insights into the interaction between SARS-CoV-2 and the host as well as potential targets for the prevention and treatment of COVID-19.
Insights
This study reveals how ubiquitination changes in host cells and SARS-CoV-2 proteins during COVID-19 infection. These findings offer new insights into virus-host interactions and potential therapeutic targets for COVID-19.
Area of Science:
- Biochemistry
- Virology
- Immunology
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, presents a significant global health challenge.
- Understanding the pathogenesis and host immune response to SARS-CoV-2 is crucial but remains incomplete.
Purpose of the Study:
- To investigate ubiquitination alterations in host cells and SARS-CoV-2 during infection.
- To identify potential therapeutic targets for COVID-19 by examining virus-host interactions.
Main Methods:
- Quantitative proteomic analysis using label-free liquid chromatography-tandem mass spectrometry.
- Identification and quantification of lysine ubiquitination sites in host proteins and viral proteins.
Main Results:
- Identified 8943 ubiquitination sites on 3086 proteins; 138 sites (104 proteins) upregulated and 828 sites (447 proteins) downregulated at 72h post-infection.
- Bioinformatics analysis indicated SARS-CoV-2 modulates host immunity via ubiquitination of key proteins (USP5, IQGAP1, TRIM28, Hsp90).
- Observed ubiquitination on 11 SARS-CoV-2 proteins involved in replication and immune evasion.
Conclusions:
- SARS-CoV-2 infection significantly alters host cell ubiquitination patterns.
- Ubiquitination of viral proteins suggests a role in virus replication and host immune response modulation.
- This research provides novel insights into SARS-CoV-2-host interactions and potential therapeutic strategies for COVID-19.
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