Show simple item record

dc.creatorSolis, Oscar
dc.creatorBeccari, Andrea R.
dc.creatorIaconis, Daniela
dc.creatorTalarico, Carmine
dc.creatorRuiz-Bedoya, Camilo A.
dc.creatorNwachukwu, Jerome C.
dc.creatorCimini, Annamaria
dc.creatorCastelli, Vanessa
dc.creatorBertini, Riccardo
dc.creatorMontopoli, Monica
dc.creatorCocetta, Veronica
dc.creatorBorocci, Stefano
dc.creatorPrandi, Ingrid G.
dc.creatorFlavahan, Kelly
dc.creatorBahr, Melissa
dc.creatorNapiorkowski, Anna
dc.creatorChillemi, Giovanni
dc.creatorOoka, Masato
dc.creatorYang, Xiaoping
dc.creatorZhang, Shiliang
dc.creatorXia, Menghang
dc.creatorZheng, Wei
dc.creatorBonaventura, Jordi
dc.creatorPomper, Jody E.
dc.creatorMorales, Marisela
dc.creatorRosenberg, Avi Z.
dc.creatorNettles, Kendall W.
dc.creatorJain, Sanjay K.
dc.creatorAllegretti, Marcello
dc.creatorMichaelides, Michael
dc.date.accessioned2022-08-29T17:20:42Z
dc.date.available2022-08-29T17:20:42Z
dc.date.issued2022-05-23
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/8058
dc.identifier.urihttp://hdl.handle.net/20.500.12613/8086
dc.identifier.urihttp://dx.doi.org/10.34944/dspace/8058
dc.description.abstractThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ERα). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ERα binding mode. In cultured cells, S DNA transfection increased ERα cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using [18F]fluoroestradiol (FES) localized lung pathology with increased ERα lung levels. Postmortem experiments in lung tissues from SARS-CoV-2-infected hamsters and humans confirmed an increase in cytoplasmic ERα expression and its colocalization with S protein in alveolar macrophages. These findings describe the discovery and characterization of a novel S-ERα interaction, imply a role for S as an NRC, and are poised to advance knowledge of SARS-CoV-2 biology, COVID-19 pathology, and mechanisms of sex differences in the pathology of infectious disease.
dc.format.extent27 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofCOVID-19 Research
dc.relation.isreferencedbybioRxiv
dc.rightsPublic Domain
dc.subjectImmunology
dc.titleThe SARS-CoV-2 spike protein binds and modulates estrogen receptors
dc.typeText
dc.type.genrePre-print
dc.description.departmentBiology
dc.relation.doihttps://doi.org/10.1101/2022.05.21.492920
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.creator.orcidCimini|0000-0002-2737-7970
dc.temple.creatorCimini, Annamaria
refterms.dateFOA2022-08-29T17:20:42Z


Files in this item

Thumbnail
Name:
Cimini-PrePrint-2022.pdf
Size:
2.710Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record