{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:37:44Z","timestamp":1771234664022,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft","award":["FOR2830 (HA 6035\/2-2)"],"award-info":[{"award-number":["FOR2830 (HA 6035\/2-2)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human leukocyte antigen class I (HLA-I) molecules present intracellular peptides on the cell surface to enable CD8+ T cells to effectively control viral infections. Many viruses disrupt this antigen presentation pathway to evade immune detection. In this study, we demonstrate that SARS-CoV-2 Nsp1 impairs both the constitutive and interferon-\u03b3 (IFN-\u03b3)-induced upregulation of HLA-I. Moreover, Nsp1 also blocks IFN-\u03b3-induced expression of HLA-II. We found that, contrary to previously published work, the early SARS-CoV-2 B 1.1.7 Alpha variant lacking the accessory protein ORF8 retained full capacity to downregulate HLA-I, comparable to an ORF8-expressing wild-type isolate. While ectopic overexpression of ORF8 could reduce HLA-I surface levels, this effect was only observed at high expression levels. In contrast, moderate expression of the viral protein Nsp1 was sufficient to potently suppress both basal and IFN-\u03b3-induced HLA-I, as well as HLA-II expression. To probe the underlying mechanism, we analyzed HLA-I-associated genes in previously published RNA-sequencing datasets and confirmed that Nsp1 reduces expression of components required for HLA-I biosynthesis and antigen processing. These findings identify Nsp1 as a key factor that impairs antigen presentation pathways, potentially contributing to the ability of SARS-CoV-2 to modulate immune recognition.<\/jats:p>","DOI":"10.3390\/v17081083","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T10:50:21Z","timestamp":1754391021000},"page":"1083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SARS-CoV-2 Nsp1 Is a Major Suppressor of HLA Class I and Class II Expression"],"prefix":"10.3390","volume":"17","author":[{"given":"Ivo","family":"Schirmeister","sequence":"first","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2116-5973","authenticated-orcid":false,"given":"Nicolas","family":"Eckert","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8415-6920","authenticated-orcid":false,"given":"Sebastian","family":"Weigang","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonas","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9365-4975","authenticated-orcid":false,"given":"Lisa","family":"Kern","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Kochs","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6335-1017","authenticated-orcid":false,"given":"Anne","family":"Halenius","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical Center University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/s41579-023-00878-2","article-title":"The evolution of SARS-CoV-2","volume":"21","author":"Markov","year":"2023","journal-title":"Nat. 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