{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:11:16Z","timestamp":1790813476513,"version":"4.1.0"},"reference-count":63,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T00:00:00Z","timestamp":1656028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["2021ff TTU 04.820 KTR8003026"],"award-info":[{"award-number":["2021ff TTU 04.820 KTR8003026"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021372","name":"Hector Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021372","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TTU 01.709; 8009701709"],"award-info":[{"award-number":["TTU 01.709; 8009701709"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Heisenberg Program and Priority Program SPP 1923"],"award-info":[{"award-number":["Heisenberg Program and Priority Program SPP 1923"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Antiviral NK cell activity is regulated through the interaction of activating and inhibitory NK cell receptors with their ligands on infected cells. HLA class I molecules serve as ligands for most killer cell immunoglobulin-like receptors (KIRs), but no HLA class I ligands for the inhibitory NK cell receptor KIR2DL5 have been identified to date. Using a NK cell receptor\/ligand screening approach, we observed no strong binding of KIR2DL5 to HLA class I or class II molecules, but confirmed that KIR2DL5 binds to the poliovirus receptor (PVR, CD155). Functional studies using primary human NK cells revealed a significantly decreased degranulation of KIR2DL5<jats:sup>+<\/jats:sup>NK cells in response to CD155-expressing target cells. We subsequently investigated the role of KIR2DL5\/CD155 interactions in HIV-1 infection, and showed that multiple HIV-1 strains significantly decreased CD155 expression levels on HIV-1-infected primary human CD4<jats:sup>+<\/jats:sup>T cells via a Nef-dependent mechanism. Co-culture of NK cells with HIV-1-infected CD4<jats:sup>+<\/jats:sup>T cells revealed enhanced anti-viral activity of KIR2DL5<jats:sup>+<\/jats:sup>NK cells against wild-type versus Nef-deficient viruses, indicating that HIV-1-mediated downregulation of CD155 renders infected cells more susceptible to recognition by KIR2DL5<jats:sup>+<\/jats:sup>NK cells. These data show that CD155 suppresses the antiviral activity of KIR2DL5<jats:sup>+<\/jats:sup>NK cells and is downmodulated by HIV-1 Nef protein as potential trade-off counteracting activating NK cell ligands, demonstrating the ability of NK cells to counteract immune escape mechanisms employed by HIV-1.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010572","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T17:39:33Z","timestamp":1656092373000},"page":"e1010572","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["HIV-1 Nef-mediated downregulation of CD155 results in viral restriction by KIR2DL5+ NK cells"],"prefix":"10.1371","volume":"18","author":[{"given":"Pia","family":"Fittje","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique","family":"H\u0153lzemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfredo F.","family":"Garcia-Beltran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Vollmers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Niehrs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri","family":"Hagemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gl\u00f2ria","family":"Martrus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"K\u00f6rner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Kirchhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sauter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5972-2997","authenticated-orcid":true,"given":"Marcus","family":"Altfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,6,24]]},"reference":[{"key":"ppat.1010572.ref001","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev-immunol-032712-100001","article-title":"Control of human viral infections by natural killer cells","author":"S Jost","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"ppat.1010572.ref002","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-immunol-020711-075005","article-title":"Controlling natural killer cell responses: integration of signals for activation and inhibition","volume":"31","author":"EO Long","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"ppat.1010572.ref003","volume-title":"The KIR Gene Cluster","author":"M Carrington","year":"2003"},{"key":"ppat.1010572.ref004","doi-asserted-by":"crossref","first-page":"571","DOI":"10.4049\/jimmunol.161.2.571","article-title":"Direct binding and functional transfer of NK cell inhibitory receptors reveal novel patterns of HLA-C allotype recognition","volume":"15","author":"CC Winter","year":"1998","journal-title":"J Immunol"},{"key":"ppat.1010572.ref005","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/1074-7613(95)90069-1","article-title":"Killer cell inhibitory receptors specific for HLA-C and HLA-B identified by direct binding and by functional transfer","volume":"3","author":"N Wagtmann","year":"1995","journal-title":"Immunity"},{"key":"ppat.1010572.ref006","article-title":"KIR2DL5: An orphan inhibitory receptor displaying complex patterns of polymorphism and expression","author":"E Cisneros","year":"2012","journal-title":"Frontiers in Immunology. 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