Open AccessThe proximal proteome of 17 SARS-CoV-2 proteins links to disrupted antiviral signaling and host translation
Author(s) -
Jordan M. Meyers,
Muthukumar Ramanathan,
Ronald L. Shanderson,
Aimee Beck,
Laura K. Donohue,
Ian Ferguson,
Margaret Guo,
Deepti Rao,
Weili Miao,
David L. Reynolds,
Xue Yang,
Yang Zhao,
Yen-Yu Yang,
Catherine A. Blish,
Yinsheng Wang,
Paul A. Khavari
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009412
Subject(s) - biology , microbiology and biotechnology , proteome , proteomics , viral protein , translation (biology) , viral pathogenesis , innate immune system , transport protein , viral replication , virology , virus , genetics , gene , immune system , messenger rna
Viral proteins localize within subcellular compartments to subvert host machinery and promote pathogenesis. To study SARS-CoV-2 biology, we generated an atlas of 2422 human proteins vicinal to 17 SARS-CoV-2 viral proteins using proximity proteomics. This identified viral proteins at specific intracellular locations, such as association of accessary proteins with intracellular membranes, and projected SARS-CoV-2 impacts on innate immune signaling, ER-Golgi transport, and protein translation. It identified viral protein adjacency to specific host proteins whose regulatory variants are linked to COVID-19 severity, including the TRIM4 interferon signaling regulator which was found proximal to the SARS-CoV-2 M protein. Viral NSP1 protein adjacency to the EIF3 complex was associated with inhibited host protein translation whereas ORF6 localization with MAVS was associated with inhibited RIG-I 2CARD-mediated IFNB1 promoter activation. Quantitative proteomics identified candidate host targets for the NSP5 protease, with specific functional cleavage sequences in host proteins CWC22 and FANCD2. This data resource identifies host factors proximal to viral proteins in living human cells and nominates pathogenic mechanisms employed by SARS-CoV-2.