An autoantigen profile of human A549 lung cells reveals viral and host etiologic molecular attributes of autoimmunity in COVID-19 Journal Article

Authors: Wang, J. Y.; Zhang, W.; Roehrl, M. W.; Roehrl, V. B.; Roehrl, M. H.
Article Title: An autoantigen profile of human A549 lung cells reveals viral and host etiologic molecular attributes of autoimmunity in COVID-19
Abstract: We aim to establish a comprehensive COVID-19 autoantigen atlas in order to understand autoimmune diseases caused by SARS-CoV-2 infection. Based on the unique affinity between dermatan sulfate and autoantigens, we identified 348 proteins from human lung A549 cells, of which 198 are known targets of autoantibodies. Comparison with current COVID data identified 291 proteins that are altered at protein or transcript level in SARS-CoV-2 infection, with 191 being known autoantigens. These known and putative autoantigens are significantly associated with viral replication and trafficking processes, including gene expression, ribonucleoprotein biogenesis, mRNA metabolism, translation, vesicle and vesicle-mediated transport, and apoptosis. They are also associated with cytoskeleton, platelet degranulation, IL-12 signaling, and smooth muscle contraction. Host proteins that interact with and that are perturbed by viral proteins are a major source of autoantigens. Orf3 induces the largest number of protein alterations, Orf9 affects the mitochondrial ribosome, and they and E, M, N, and Nsp proteins affect protein localization to membrane, immune responses, and apoptosis. Phosphorylation and ubiquitination alterations by viral infection define major molecular changes in autoantigen origination. This study provides a large list of autoantigens as well as new targets for future investigation, e.g., UBA1, UCHL1, USP7, CDK11A, PRKDC, PLD3, PSAT1, RAB1A, SLC2A1, platelet activating factor acetylhydrolase, and mitochondrial ribosomal proteins. This study illustrates how viral infection can modify host cellular proteins extensively, yield diverse autoantigens, and trigger a myriad of autoimmune sequelae. Our work provides a rich resource for studies into “long COVID” and related autoimmune sequelae. © 2021 The Authors
Keywords: lung; autoantigens; autoimmunity; atlas; resource; covid-19
Journal Title: Journal of Autoimmunity
Volume: 120
ISSN: 0896-8411
Publisher: Academic Press, Elsevier Inc  
Date Published: 2021-06-01
Start Page: 102644
Language: English
DOI: 10.1016/j.jaut.2021.102644
PROVIDER: scopus
PMCID: PMC8075847
PUBMED: 33971585
Notes: Article -- Export Date: 1 June 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Michael H Roehrl
    107 Roehrl