Multi-cell type proteomic profiling reveals desensitization of SARS-CoV-2-infected cells to interferon treatment

ABSTRACT: SARS-CoV-2, the coronavirus behind the ongoing pandemic, manifests itself in a broad array of symptoms involving various body organs, such as lungs, intestine, kidneys, heart, liver, and brain. To investigate how SARS-CoV-2 navigates disparate organs and alters their biology, we engineered a panel of phenotypically diverse human cell lines representing different organs that support efficient virus infection. We leveraged these infection models to profile tissue-specific host responses to SARS-CoV-2 infection by global proteomic analyses. This uncovered broad as well as cell type-specific perturbations of cellular proteins, several of which we subsequently validated by an orthogonal approach. Our detailed follow-up investigation of a number of proteins in different cell types, including a stem cell-derived model of virus infection, revealed almost complete desensitization of SARS-CoV-2-infected cells to interferon treatment. These findings elucidate the immune evasion mechanisms of SARS-CoV-2 and have implications for the currently evaluated antiviral regimens involving interferon (148).

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Heart, Brain, Lung, Liver, Colon, Kidney

SUBMITTER: Christian Heckendorf  

LAB HEAD: Mohsan Saeed

PROVIDER: PXD022027 | Pride | 2021-07-27

REPOSITORIES: Pride