{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T08:58:22Z","timestamp":1785229102488,"version":"3.55.0"},"reference-count":240,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Human cytomegalovirus (CMV) remains a significant infectious complication after kidney transplantation, reflecting gaps in the understanding of the molecular and immunological mechanisms regulating the transition from latency to productive infection. Following primary infection, CMV establishes lifelong latency in hematopoietic and myeloid lineage cells, maintained by viral chromatin repression and robust CMV-specific immune surveillance. CMV reactivation is associated with graft dysfunction, increased risk of rejection, opportunistic infections, and reduced patient survival. In kidney transplantation, CMV reactivation is driven by the interplay between tissue injury, inflammation, and immunosuppression. Ischemia\u2013reperfusion injury and peri-operative stress produce reactive oxygen species, DNA damage, and pro-inflammatory cytokines (e.g., TNF-\u03b1, IL-6), which activate transcription factors such as NF-\u03baB and AP-1. These factors regulate the CMV major immediate-early promoter (MIEP), thereby triggering lytic viral gene expression. At the same time, immunosuppressive therapies impair antiviral immune surveillance and, in some cases, induce cytokine release, potentially contributing to the pro-inflammatory environment that favors viral reactivation. In this review, we summarize current molecular and immunologic mechanisms governing CMV latency and reactivation with a focus on how immunosuppressive strategies and injury-associated pathways converge to promote CMV reactivation. We also discuss implications of risk stratification and the development of targeted therapeutic strategies to prevent CMV reactivation in kidney transplant recipients (KTRs).<\/jats:p>","DOI":"10.3390\/ijms27156727","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:55:41Z","timestamp":1785225341000},"page":"6727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms and Determinants of CMV Reactivation in Kidney Transplantation"],"prefix":"10.3390","volume":"27","author":[{"given":"Ruchi","family":"Naik","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2033-279X","authenticated-orcid":false,"given":"Walaa","family":"Dabbas","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"3rd","given":"Benito","family":"Veldepenas","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of Surgery, University of Illinois Chicago, Chicago, IL 60612, USA"},{"name":"Department of Pharmacy Practice, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrius","family":"Harvell","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fares","family":"Eshac","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Minicucci","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6277-4405","authenticated-orcid":false,"given":"Mary","family":"Hummel","sequence":"additional","affiliation":[{"name":"Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6469-5778","authenticated-orcid":false,"given":"Zheng Jenny","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gallon","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"},{"name":"Division of Transplantation, Department of Surgery, University of Illinois Chicago, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6095-2797","authenticated-orcid":false,"given":"Eleonora","family":"Forte","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Forte, E., Zhang, Z., Thorp, E.B., and Hummel, M. 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