{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Raviola S"],"funding":["Università degli Studi di Torino","Università degli Studi di Torino (University of Turin)"],"pagination":["292"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10924099"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(1)"],"pubmed_abstract":["Human cytomegalovirus (HCMV) is an opportunistic pathogen causing severe diseases in immunosuppressed individuals. To replicate its double-stranded DNA genome, HCMV induces profound changes in cellular homeostasis that may resemble senescence. However, it remains to be determined whether HCMV-induced senescence contributes to organ-specific pathogenesis. Here, we show a direct cytopathic effect of HCMV on primary renal proximal tubular epithelial cells (RPTECs), a natural setting of HCMV disease. We find that RPTECs are fully permissive for HCMV replication, which endows them with an inflammatory gene signature resembling the senescence-associated secretory phenotype (SASP), as confirmed by the presence of the recently established SenMayo gene set, which is not observed in retina-derived epithelial (ARPE-19) cells. Although HCMV-induced senescence is not cell-type specific, as it can be observed in both RPTECs and human fibroblasts (HFFs), only infected RPTECs show downregulation of LAMINB1 and KI67 mRNAs, and enhanced secretion of IL-6 and IL-8, which are well-established hallmarks of senescence. Finally, HCMV-infected RPTECs have the ability to trigger a senescence/inflammatory loop in an IL-6-dependent manner, leading to the development of a similar senescence/inflammatory phenotype in neighboring uninfected cells. Overall, our findings raise the intriguing possibility that this unique inflammatory loop contributes to HCMV-related pathogenesis in the kidney."],"journal":["Communications biology"],"pubmed_title":["Human cytomegalovirus infection triggers a paracrine senescence loop in renal epithelial cells."],"pmcid":["PMC10924099"],"funding_grant_id":["PoC - TOINPROVE/2020"],"pubmed_authors":["Lo Cigno I","Favero F","Chandel S","Raviola S","Lacarbonara D","Gariglio M","Caneparo V","Griffante G","Landolfo S","Trisolini E","Cantaluppi V","Boldorini R","De Andrea M","Cora D","Iannucci A","Pasquero S"],"additional_accession":[]},"is_claimable":false,"name":"Human cytomegalovirus infection triggers a paracrine senescence loop in renal epithelial cells.","description":"Human cytomegalovirus (HCMV) is an opportunistic pathogen causing severe diseases in immunosuppressed individuals. To replicate its double-stranded DNA genome, HCMV induces profound changes in cellular homeostasis that may resemble senescence. However, it remains to be determined whether HCMV-induced senescence contributes to organ-specific pathogenesis. Here, we show a direct cytopathic effect of HCMV on primary renal proximal tubular epithelial cells (RPTECs), a natural setting of HCMV disease. We find that RPTECs are fully permissive for HCMV replication, which endows them with an inflammatory gene signature resembling the senescence-associated secretory phenotype (SASP), as confirmed by the presence of the recently established SenMayo gene set, which is not observed in retina-derived epithelial (ARPE-19) cells. Although HCMV-induced senescence is not cell-type specific, as it can be observed in both RPTECs and human fibroblasts (HFFs), only infected RPTECs show downregulation of LAMINB1 and KI67 mRNAs, and enhanced secretion of IL-6 and IL-8, which are well-established hallmarks of senescence. Finally, HCMV-infected RPTECs have the ability to trigger a senescence/inflammatory loop in an IL-6-dependent manner, leading to the development of a similar senescence/inflammatory phenotype in neighboring uninfected cells. Overall, our findings raise the intriguing possibility that this unique inflammatory loop contributes to HCMV-related pathogenesis in the kidney.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-22T00:58:41.767Z","creation":"2025-04-22T00:58:41.767Z"},"accession":"S-EPMC10924099","cross_references":{"pubmed":["38459109"],"doi":["10.1038/s42003-024-05957-5"]}}