Ubiquitin-Modified Proteome of SARS-CoV-2-Infected Host Cells Reveals Insights into Virus–Host Interaction and Pathogenesis

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.