{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:07:05Z","timestamp":1792440425306,"version":"4.5.0"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research, University of Ferrara","award":["FAR 2024"],"award-info":[{"award-number":["FAR 2024"]}]},{"name":"European Union\u2014Next Generation EU","award":["2022WXLMS9"],"award-info":[{"award-number":["2022WXLMS9"]}]},{"name":"European Union\u2014Next Generation EU","award":["mission 4"],"award-info":[{"award-number":["mission 4"]}]},{"name":"European Union\u2014Next Generation EU","award":["CUP F53D23000980006"],"award-info":[{"award-number":["CUP F53D23000980006"]}]},{"name":"RIPREI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Natural killer (NK) cells are central to antiviral immunity through a balance of activating and inhibitory receptors, including killer immunoglobulin-like receptors (KIRs). We have previously observed that an increased frequency of the inhibitory receptor KIR2DL2 and its ligand HLA-C1 is associated with heightened susceptibility to human herpesvirus (HHV) infection, supporting a role for KIR-mediated NK cell regulation in host\u2013virus interactions. We investigated whether the co-infection of SARS-CoV-2 and human herpesvirus 6 (HHV-6) might be connected to the expression of KIR2DL2\/HLA-C1. We analyzed 110 SARS-CoV-2-positive subjects and 109 SARS-CoV-2-negative subjects for the KIR2DL2 and HLA-C1 genotype and for HHV-6A\/B reactivation in plasma samples. SARS-CoV-2-positive subjects showed a significantly higher frequency of the KIR2DL2\/HLA-C1 haplotype and increased reactivation of HHV-6A. Among deceased and comorbid patients, the co-occurrence of the KIR2DL2\/HLA-C1 haplotype and HHV-6A DNAemia was more frequent, particularly in those with cardiovascular disorders. These findings suggest that the KIR2DL2\/HLA-C1 haplotype might promote NK cell inhibition, facilitating HHV-6A persistence and contributing to immune dysregulation during SARS-CoV-2 infection. The combined presence of KIR2DL2\/HLA-C1 and HHV-6A may, therefore, represent a molecular signature of COVID-19 outcomes.<\/jats:p>","DOI":"10.3390\/microorganisms14010235","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:24:34Z","timestamp":1768901074000},"page":"235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["SARS-CoV-2 Infection Associated with HHV-6A Reactivation and an Inhibitory KIR2DL2\/HLA-C1 Immunogenetic Profile"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9246-136X","authenticated-orcid":false,"given":"Sabrina","family":"Rizzo","sequence":"first","affiliation":[{"name":"Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3032-3245","authenticated-orcid":false,"given":"Matteo","family":"Ferraresi","sequence":"additional","affiliation":[{"name":"Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7227-7939","authenticated-orcid":false,"given":"Giovanni","family":"Strazzabosco","sequence":"additional","affiliation":[{"name":"Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Baroni","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology (SVEB), University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3372-2758","authenticated-orcid":false,"given":"Juana Maria","family":"Sanz","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Passaro","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-9561","authenticated-orcid":false,"given":"Daria","family":"Bortolotti","sequence":"additional","affiliation":[{"name":"Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-9126","authenticated-orcid":false,"given":"Roberta","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4652-5550","authenticated-orcid":false,"given":"Giovanna","family":"Schiuma","sequence":"additional","affiliation":[{"name":"Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus from Patients with Pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. 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