{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:19:04Z","timestamp":1790651944435,"version":"4.1.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["Transpl. Int."],"abstract":"<jats:p>Herpesviruses are able to modulate adaptive T-cell-mediated responses to establish latency within the host. Reactivation of herpes simplex virus (HSV)-1\/2 and varicella zoster virus (VZV) is a frequent and potentially serious complication among kidney transplant recipients (KTRs). The ability of clinical criteria to identify KTRs at increased risk of \u03b1-herpesvirus (HSV\/VZV) infection is limited. We investigated the effect of two single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte antigen 4 <jats:italic>(CTLA4)<\/jats:italic> gene in a single-center cohort of 204 KTRs. After a median follow-up of 3.1 years, 34 of them (16.7%) experienced 22 episodes of zoster and 15 episodes of HSV-1\/2 infection. Homozygous carriers of the minor allele of rs231775 had a higher cumulative incidence of \u03b1-herpesvirus infection (23.5% for GG versus 7.6% for AA\/AG carriers; <jats:italic>P<\/jats:italic>-value = 0.011) and a lower infection-free survival (log-rank <jats:italic>P<\/jats:italic>-value = 0.037). After multivariable adjustment by clinical factors (including use of valganciclovir prophylaxis and acute rejection as time-dependent variables), the GG genotype of <jats:italic>CTLA4<\/jats:italic> (rs231775) SNP was associated to the study outcome (adjusted hazard ratio: 3.21; 95% confidence interval: 1.44\u20137.16). In conclusion, genetic polymorphisms in the co-inhibitory T-cell receptor CTLA-4 may be detrimental for the immune control of latent HSV\/VZV infection in KTRs.<\/jats:p>","DOI":"10.3389\/ti.2025.14648","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T05:10:21Z","timestamp":1747804221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["CTLA4 Single-Nucleotide Polymorphisms Influence the Risk of HSV and VZV Infection in Kidney Transplant Recipients: A Prospective Cohort Study"],"prefix":"10.3389","volume":"38","author":[{"given":"Natalia","family":"Redondo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Rodr\u00edguez-Goncer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Ruiz-Merlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"L\u00f3pez-Medrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Polanco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Hern\u00e1ndez-Vicente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"San Juan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amado","family":"Andr\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Aguado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Fern\u00e1ndez-Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e13526","DOI":"10.1111\/ctr.13526","article-title":"Herpes Simplex Virus Infections in Solid Organ Transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice","volume":"33","author":"Lee","year":"2019","journal-title":"Clin Transpl"},{"key":"B2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/ajt.12003","article-title":"Varicella Zoster Virus (VZV) and Herpes Simplex Virus (HSV) in Solid Organ Transplant Patients","volume":"13","author":"Zuckerman","year":"2013","journal-title":"Am J Transpl"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e13622","DOI":"10.1111\/ctr.13622","article-title":"Varicella Zoster Virus in Solid Organ Transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice","volume":"33","author":"Pergam","year":"2019","journal-title":"Clin Transpl"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1111\/ajt.14192","article-title":"Preventive Strategies against Cytomegalovirus and Incidence of Alpha-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study","volume":"17","author":"Martin-Gandul","year":"2017","journal-title":"Am J Transpl"},{"key":"B5","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1111\/tri.13076","article-title":"Herpes Zoster in Kidney Transplant Recipients: Protective Effect of Anti-Cytomegalovirus Prophylaxis and Natural Killer Cell Count. 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