{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T07:52:23Z","timestamp":1786261943654,"version":"build-2736575974"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01AI165075"],"award-info":[{"award-number":["P01AI165075"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI164565"],"award-info":[{"award-number":["UM1AI164565"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI147845"],"award-info":[{"award-number":["R01AI147845"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30 AI060354"],"award-info":[{"award-number":["P30 AI060354"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,10,11]]},"abstract":"<jats:p>\n                    Viruses employ a variety of strategies to escape or counteract immune responses, including depletion of cell surface major histocompatibility complex class I (MHC-I), that would ordinarily present viral peptides to CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T cells. As part of a screen to elucidate biological activities associated with individual severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral proteins, we found that ORF7a reduced cell surface MHC-I levels by approximately fivefold. Nevertheless, in cells infected with SARS-CoV-2, surface MHC-I levels were reduced even in the absence of ORF7a, suggesting additional mechanisms of MHC-I down-regulation. ORF7a proteins from a sample of sarbecoviruses varied in their ability to induce MHC-I down-regulation and, unlike SARS-CoV-2, the ORF7a protein from SARS-CoV lacked MHC-I downregulating activity. A single amino acid at position 59 (T\/F) that is variable among sarbecovirus ORF7a proteins governed the difference in MHC-I downregulating activity. SARS-CoV-2 ORF7a physically associated with the MHC-I heavy chain and inhibited the presentation of expressed antigen to CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Specifically, ORF7a prevented the assembly of the MHC-I peptide loading complex and caused retention of MHC-I in the endoplasmic reticulum. The differential ability of ORF7a proteins to function in this way might affect sarbecovirus dissemination and persistence in human populations, particularly those with infection- or vaccine-elicited immunity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2209042119","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T13:48:17Z","timestamp":1663854497000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":21,"title":["Inhibition of major histocompatibility complex-I antigen presentation by sarbecovirus ORF7a proteins"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7427-3771","authenticated-orcid":false,"given":"Fengwen","family":"Zhang","sequence":"first","affiliation":[{"name":"Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3931-4704","authenticated-orcid":false,"given":"Trinity M.","family":"Zang","sequence":"additional","affiliation":[{"name":"Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Infectious Disease Division, Weill Cornell Medicine, New York, NY; 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8641-7824","authenticated-orcid":false,"given":"Xiao","family":"Lei","sequence":"additional","affiliation":[{"name":"Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3217-4713","authenticated-orcid":false,"given":"Dennis C.","family":"Copertino","sequence":"additional","affiliation":[{"name":"Infectious Disease Division, Weill Cornell Medicine, New York, NY; 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talia M.","family":"Mota","sequence":"additional","affiliation":[{"name":"Infectious Disease Division, Weill Cornell Medicine, New York, NY; 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-7238","authenticated-orcid":false,"given":"Julie","family":"Boucau","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfredo F.","family":"Garcia-Beltran","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139"},{"name":"Department of Pathology, Massachusetts General Hospital, Boston, MA 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Brad","family":"Jones","sequence":"additional","affiliation":[{"name":"Infectious Disease Division, Weill Cornell Medicine, New York, NY; 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2368-3719","authenticated-orcid":false,"given":"Paul D.","family":"Bieniasz","sequence":"additional","affiliation":[{"name":"Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065"},{"name":"Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17665-9"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108234"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1780953"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.61312"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd0831"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04005-0"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.11.007"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.01.014"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.16.1.323"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2575"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2016.02.007"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0396-338"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2008-3"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2286-9"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","unstructured":"E. M. N. Laurent Global BioID-based SARS-CoV-2 proteins proximal interactome unveils novel ties between viral polypeptides and host factors involved in multiple COVID19-associated mechanisms. bioRxiv [Preprint] (2020). doi.org\/10.1101\/2020.08.28.272955. Accessed 30 August 2020.","DOI":"10.1101\/2020.08.28.272955"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2024202118"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","unstructured":"M. Moriyama C. Lucas V. S. Monteiro A. Iwasaki SARS-CoV-2 variants do not evolve to promote further escape from MHC-I recognition. bioRxiv [Preprint] (2022). doi.org\/10.1101\/2022.05.04.490614. Accessed 5 May 2022.","DOI":"10.1101\/2022.05.04.490614"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09907"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc8665"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1998.tb02994.x"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002510100353"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.09.005"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03098"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-03-0218"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(79)90210-1"},{"key":"e_1_3_4_27_2","first-page":"Unit 17.13A","article-title":"Endoglycosidase and glycoamidase release of N-linked glycans","volume":"17","author":"Freeze H. H.","year":"2010","unstructured":"H. H. Freeze, C. Kranz, Endoglycosidase and glycoamidase release of N-linked glycans. Curr. Protoc. Mol. Biol. Chapter 17, Unit 17.13A (2010).","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04186-8"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03207-w"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.04.037"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00464-3"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26910-8"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.04.004"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97555"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2209042119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T08:31:10Z","timestamp":1695285070000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2209042119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,22]]},"references-count":34,"journal-issue":{"issue":"41","published-print":{"date-parts":[[2022,10,11]]}},"alternative-id":["10.1073\/pnas.2209042119"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2209042119","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.05.25.493467","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,22]]},"assertion":[{"value":"2022-05-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2209042119"}}