{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T07:12:43Z","timestamp":1772262763542,"version":"3.50.1"},"reference-count":151,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Herpesviruses, including the roseoloviruses, have been linked to autoimmune disease. The ubiquitous and chronic nature of these infections have made it difficult to establish a causal relationship between acute infection and subsequent development of autoimmunity. We have shown that murine roseolovirus (MRV), which is highly related to human roseoloviruses, induces thymic atrophy and disruption of central tolerance after neonatal infection. Moreover, neonatal MRV infection results in development of autoimmunity in adult mice, long after resolution of acute infection. This suggests that MRV induces durable immune dysregulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the current studies, we utilized single-cell RNA sequencing (scRNAseq) to study the tropism of MRV in the thymus and determine cellular processes in the thymus that were disrupted by neonatal MRV infection. We then utilized tropism data to establish a cell culture system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Herein, we describe how MRV alters the thymic transcriptome during acute neonatal infection. We found that MRV infection resulted in major shifts in inflammatory, differentiation and cell cycle pathways in the infected thymus. We also observed shifts in the relative number of specific cell populations. Moreover, utilizing expression of late viral transcripts as a proxy of viral replication, we identified the cellular tropism of MRV in the thymus. This approach demonstrated that double negative, double positive, and CD4 single positive thymocytes, as well as medullary thymic epithelial cells were infected by MRV <jats:italic>in vivo<\/jats:italic>. Finally, by applying pseudotime analysis to viral transcripts, which we refer to as \u201cpseudokinetics,\u201d we identified viral gene transcription patterns associated with specific cell types and infection status. We utilized this information to establish the first cell culture systems susceptible to MRV infection <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our research provides the first complete picture of roseolovirus tropism in the thymus after neonatal infection. Additionally, we identified major transcriptomic alterations in cell populations in the thymus during acute neonatal MRV infection. These studies offer important insight into the early events that occur after neonatal MRV infection that disrupt central tolerance and promote autoimmune disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1375508","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T05:45:54Z","timestamp":1717479954000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic profiling of thymic dysregulation and viral tropism after neonatal roseolovirus infection"],"prefix":"10.3389","volume":"15","author":[{"given":"Andrei","family":"Belean","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eden","family":"Xue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Cisneros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisha D. O.","family":"Roberson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Paley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarin M.","family":"Bigley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"782","DOI":"10.3390\/v15030782","article-title":"The role of viral infections in the onset of autoimmune diseases","volume":"15","author":"Sundaresan","year":"2023","journal-title":"Viruses"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211403","article-title":"Disruption of thymic central tolerance by infection with murine roseolovirus induces autoimmune gastritis","volume":"219","author":"Bigley","year":"2022","journal-title":"J Exp Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1126\/science.abj8222","article-title":"Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis","volume":"375","author":"Bjornevik","year":"2022","journal-title":"Science"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nri2527","article-title":"Antiviral immune responses: triggers of or triggered by autoimmunity","volume":"9","author":"Munz","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1128\/CMR.19.1.80-94.2006","article-title":"Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease","volume":"19","author":"Fujinami","year":"2006","journal-title":"Clin Microbiol Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-011-8294-7","article-title":"Molecular mimicry as a mechanism of autoimmune disease","volume":"42","author":"Cusick","year":"2012","journal-title":"Clin Rev Allergy Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04432-7","article-title":"Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM","volume":"603","author":"Lanz","year":"2022","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2009.05.010","article-title":"Reactivation of human herpesvirus 6 (HHV-6) infection in patients with connective tissue diseases","volume":"46","author":"Broccolo","year":"2009","journal-title":"J Clin Virol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"867389","DOI":"10.1155\/2013\/867389","article-title":"Possible role of human herpesvirus 6 as a trigger of autoimmune disease","volume":"2013","author":"Broccolo","year":"2013","journal-title":"ScientificWorldJournal"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.23670","article-title":"Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases","volume":"85","author":"Broccolo","year":"2013","journal-title":"J Med Virol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e1002951","DOI":"10.1371\/journal.ppat.1002951","article-title":"Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto\u2019s thyroiditis","volume":"8","author":"Caselli","year":"2012","journal-title":"PloS Pathog"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s12985-016-0672-6","article-title":"HHV-6A in vitro infection of thyrocytes and T cells alters the expression of miRNA associated to autoimmune thyroiditis","volume":"14","author":"Caselli","year":"2017","journal-title":"Virol J"},{"key":"B13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3390\/microorganisms8010039","article-title":"HHV-6A infection and systemic sclerosis: clues of a possible association","volume":"8","author":"Caselli","year":"2019","journal-title":"Microorganisms"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.3390\/v11121108","article-title":"Comparative analysis of roseoloviruses in humans, pigs, mice, and other species","volume":"11","author":"Denner","year":"2019","journal-title":"Viruses"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02463-16","article-title":"A murine herpesvirus closely related to ubiquitous human herpesviruses causes T-cell depletion","volume":"91","author":"Patel","year":"2017","journal-title":"J Virol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700982","article-title":"CD8(+) T cells prevent lethality from neonatal murine roseolovirus infection","volume":"199","author":"Patel","year":"2017","journal-title":"J Immunol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s13024-021-00514-8","article-title":"Murine roseolovirus does not accelerate amyloid-beta pathology and human roseoloviruses are not over-represented in Alzheimer disease brains","volume":"17","author":"Bigley","year":"2022","journal-title":"Mol Neurodegener"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e62","DOI":"10.1371\/journal.ppat.0020062","article-title":"The thymus is a common target organ in infectious diseases","volume":"2","author":"Savino","year":"2006","journal-title":"PloS Pathog"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00457-z","article-title":"T cell regeneration after immunological injury","volume":"21","author":"Velardi","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1993.18","article-title":"Characterization of thymic involution induced by murine cytomegalovirus infection","volume":"71","author":"Price","year":"1993","journal-title":"Immunol Cell Biol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"40793","DOI":"10.1038\/srep40793","article-title":"Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma","volume":"7","author":"Majumdar","year":"2017","journal-title":"Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199606001-00005","article-title":"Thymocyte and thymic microenvironment alterations during a systemic HIV infection in a severe combined immunodeficient mouse model","volume":"10","author":"Autran","year":"1996","journal-title":"AIDS"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1913776117","article-title":"Chronic virus infection drives CD8 T cell-mediated thymic destruction and impaired negative selection","volume":"117","author":"Elsaesser","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00428","article-title":"Differential Expression of microRNAs in Thymic Epithelial Cells from Trypanosoma cruzi Acutely Infected Mice: putative Role in Thymic Atrophy","volume":"6","author":"Linhares-Lacerda","year":"2015","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1038\/s41598-020-58135-y","article-title":"Zika virus targets the human thymic epithelium","volume":"10","author":"Messias","year":"2020","journal-title":"Sci Rep"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.3.2212-2221.1999","article-title":"Measles virus infection induces terminal differentiation of human thymic epithelial cells","volume":"73","author":"Valentin","year":"1999","journal-title":"J Virol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"279","DOI":"10.3390\/genes11030279","article-title":"Housekeeping gene expression in the fetal and neonatal murine thymus following coxsackievirus B4 infection","volume":"11","author":"Halouani","year":"2020","journal-title":"Genes (Basel)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.3390\/microorganisms9071537","article-title":"Coxsackievirus B4 transplacental infection severely disturbs central tolerogenic mechanisms in the fetal thymus","volume":"9","author":"Halouani","year":"2021","journal-title":"Microorganisms"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.3390\/microorganisms9061177","article-title":"Effect of coxsackievirus B4 infection on the thymus: elucidating its role in the pathogenesis of type 1 diabetes","volume":"9","author":"Alhazmi","year":"2021","journal-title":"Microorganisms"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.12.1953","article-title":"Human herpesvirus 6 (HHV-6) causes severe thymocyte depletion in SCID-hu Thy\/Liv mice","volume":"189","author":"Gobbi","year":"1999","journal-title":"J Exp Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.02.007","article-title":"Thymus transplantation","volume":"135","author":"Markert","year":"2010","journal-title":"Clin Immunol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1016\/j.jaci.2017.03.020","article-title":"Thymus transplantation for complete DiGeorge syndrome: European experience","volume":"140","author":"Davies","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00343.x","article-title":"Regulation of T-cell progenitor survival and cell-cycle entry by the pre-T-cell receptor","volume":"209","author":"Aifantis","year":"2006","journal-title":"Immunol Rev"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154008","article-title":"Mechanisms of T cell development and transformation","volume":"27","author":"Koch","year":"2011","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1242\/dev.178582","article-title":"Canonical Notch signaling controls the early thymic epithelial progenitor cell state and emergence of the medullary epithelial lineage in fetal thymus development","volume":"147","author":"Liu","year":"2020","journal-title":"Development"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.69975","article-title":"Notch-induced endoplasmic reticulum-associated degradation governs mouse thymocyte beta-selection","volume":"10","author":"Liu","year":"2021","journal-title":"Elife"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00358.x","article-title":"TCR and Notch signaling in CD4 and CD8 T-cell development","volume":"209","author":"Laky","year":"2006","journal-title":"Immunol Rev"},{"key":"B38","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.coi.2008.03.004","article-title":"Notch signaling in CD4 and CD8 T cell development","volume":"20","author":"Laky","year":"2008","journal-title":"Curr Opin Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500821","article-title":"Transcription factor 7 limits regulatory T cell generation in the thymus","volume":"195","author":"Barra","year":"2015","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.3.1137","article-title":"Involvement of transcription factors TCF-1 and GATA-3 in the initiation of the earliest step of T cell development in the thymus","volume":"184","author":"Hattori","year":"1996","journal-title":"J Exp Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.8.3984","article-title":"Critical involvement of Tcf-1 in expansion of thymocytes","volume":"161","author":"Schilham","year":"1998","journal-title":"J Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-012-9367-y","article-title":"beta-catenin\/TCF-1 pathway in T cell development and differentiation","volume":"7","author":"Ma","year":"2012","journal-title":"J Neuroimmune Pharmacol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.884569","article-title":"Transcriptional regulation of early T-lymphocyte development in thymus","volume":"13","author":"Bao","year":"2022","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2010.08.003","article-title":"Life and death in the thymus\u2013cell death signaling during T cell development","volume":"22","author":"Hernandez","year":"2010","journal-title":"Curr Opin Cell Biol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"190187","DOI":"10.1098\/rsob.190187","article-title":"Notch signalling in T cell homeostasis and differentiation","volume":"9","author":"Brandstadter","year":"2019","journal-title":"Open Biol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040394","article-title":"Maintenance of T cell specification and differentiation requires recurrent notch receptor-ligand interactions","volume":"200","author":"Schmitt","year":"2004","journal-title":"J Exp Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5230","article-title":"Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation","volume":"172","author":"Ciofani","year":"2004","journal-title":"J Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ni1234","article-title":"Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism","volume":"6","author":"Ciofani","year":"2005","journal-title":"Nat Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.06.007","article-title":"Immature CD8 single-positive thymocytes are a molecularly distinct subpopulation, selectively dependent on BRD4 for their differentiation","volume":"24","author":"Gegonne","year":"2018","journal-title":"Cell Rep"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-01-477349","article-title":"TCF-1 mediates repression of Notch pathway in T lineage-committed early thymocytes","volume":"121","author":"Yu","year":"2013","journal-title":"Blood"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060474","article-title":"Differential synergy of Notch and T cell receptor signaling determines alphabeta versus gammadelta lineage fate","volume":"203","author":"Garbe","year":"2006","journal-title":"J Exp Med"},{"key":"B52","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1093\/intimm\/dxq457","article-title":"Immature single-positive CD8+ thymocytes represent the transition from Notch-dependent to Notch-independent T-cell development","volume":"23","author":"Xiong","year":"2011","journal-title":"Int Immunol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13073-021-00861-7","article-title":"Development of double-positive thymocytes at single-cell resolution","volume":"13","author":"Li","year":"2021","journal-title":"Genome Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2023.0015","article-title":"T cell development and function","volume":"26","author":"Adu-Berchie","year":"2023","journal-title":"Rejuvenation Res"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e2250202","DOI":"10.1002\/eji.202250202","article-title":"T-cell selection in the thymus: New routes toward the identification of the self-peptide ligandome presented by thymic epithelial cells","volume":"53","author":"Sousa","year":"2023","journal-title":"Eur J Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/nri3667","article-title":"Positive and negative selection of the T cell repertoire: what thymocytes see (and don\u2019t see)","volume":"14","author":"Klein","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080866","article-title":"Clonal deletion of thymocytes can occur in the cortex with no involvement of the medulla","volume":"205","author":"McCaughtry","year":"2008","journal-title":"J Exp Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.07.010","article-title":"The mechanisms of T cell selection in the thymus","volume":"38","author":"Takaba","year":"2017","journal-title":"Trends Immunol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"3930750","DOI":"10.1155\/2018\/3930750","article-title":"The role of autoimmune regulator (AIRE) in peripheral tolerance","volume":"2018","author":"Zhao","year":"2018","journal-title":"J Immunol Res"},{"key":"B60","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/imm.12831","article-title":"Update on Aire and thymic negative selection","volume":"153","author":"Passos","year":"2018","journal-title":"Immunology"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0128-9","article-title":"Thymic tolerance as a key brake on autoimmunity","volume":"19","author":"Cheng","year":"2018","journal-title":"Nat Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(88)90262-0","article-title":"Mouse thymic virus (MTLV; murid herpesvirus 3) infection in athymic nude mice: evidence for a T lymphocyte requirement","volume":"163","author":"Morse","year":"1988","journal-title":"Virology"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.9.5309","article-title":"Virus and autoimmunity: induction of autoimmune disease in mice by mouse T lymphotropic virus (MTLV) destroying CD4+ T cells","volume":"162","author":"Morse","year":"1999","journal-title":"J Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.10.4475-4481.2001","article-title":"Herpesvirus lytic replication and the cell cycle: arresting new developments","volume":"75","author":"Flemington","year":"2001","journal-title":"J Virol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-013-1826-0","article-title":"Cell cycle perturbations induced by human herpesvirus 6 infection and their effect on virus replication","volume":"159","author":"Li","year":"2014","journal-title":"Arch Virol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2016.11.009","article-title":"Herpesviruses and their host cells: A successful liaison","volume":"25","author":"Adler","year":"2017","journal-title":"Trends Microbiol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00396","article-title":"Breaking bad: how viruses subvert the cell cycle","volume":"8","author":"Fan","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2014.08.005","article-title":"The role of DNA repair in herpesvirus pathogenesis","volume":"104","author":"Brown","year":"2014","journal-title":"Genomics"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.02.009","article-title":"Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity","author":"Knipe","year":"2015","journal-title":"Virology"},{"key":"B70","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.3390\/cells10082122","article-title":"Innate immune responses to herpesvirus infection","volume":"10","author":"O\u2019Connor","year":"2021","journal-title":"Cells"},{"key":"B71","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.vetmic.2010.02.017","article-title":"Herpesviruses and immunity: the art of evasion","volume":"143","author":"Griffin","year":"2010","journal-title":"Vet Microbiol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-100114-054839","article-title":"Modulation of the translational landscape during herpesvirus infection","volume":"2","author":"Glaunsinger","year":"2015","journal-title":"Annu Rev Virol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1007\/s11262-019-01643-5","article-title":"Interactions between the transcription and replication machineries regulate the RNA and DNA synthesis in the herpesviruses","volume":"55","author":"Boldogkoi","year":"2019","journal-title":"Virus Genes"},{"key":"B74","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3390\/v11020119","article-title":"Chewing the fat: the conserved ability of DNA viruses to hijack cellular lipid metabolism","volume":"11","author":"Lange","year":"2019","journal-title":"Viruses"},{"key":"B75","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.antiviral.2016.02.007","article-title":"Impact of a cytomegalovirus kinase inhibitor on infection and neuronal progenitor cell differentiation","volume":"129","author":"Bigley","year":"2016","journal-title":"Antiviral Res"},{"key":"B76","doi-asserted-by":"publisher","first-page":"101539","DOI":"10.1016\/j.trim.2022.101539","article-title":"Cytomegalovirus and other herpesviruses after hematopoietic cell and solid organ transplantation: From antiviral drugs to virus-specific T cells","volume":"71","author":"Ivana","year":"2022","journal-title":"Transpl Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02161-09","article-title":"Human cytomegalovirus infection causes premature and abnormal differentiation of human neural progenitor cells","volume":"84","author":"Luo","year":"2010","journal-title":"J Virol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00351-15","article-title":"Human cytomegalovirus infection dysregulates the localization and stability of NICD1 and jag1 in neural progenitor cells","volume":"89","author":"Li","year":"2015","journal-title":"J Virol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"e1006542","DOI":"10.1371\/journal.ppat.1006542","article-title":"Human cytomegalovirus IE1 downregulates Hes1 in neural progenitor cells as a potential E3 ubiquitin ligase","volume":"13","author":"Liu","year":"2017","journal-title":"PloS Pathog"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00013-18","article-title":"Defining the transcriptional landscape during cytomegalovirus latency with single-cell RNA sequencing","volume":"9","author":"Shnayder","year":"2018","journal-title":"mBio"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06704-2","article-title":"Latent human herpesvirus 6 is reactivated in CAR T cells","volume":"623","author":"Lareau","year":"2023","journal-title":"Nature"},{"key":"B82","doi-asserted-by":"publisher","first-page":"110653","DOI":"10.1016\/j.celrep.2022.110653","article-title":"Temporal dynamics of HCMV gene expression in lytic and latent infections","volume":"39","author":"Rozman","year":"2022","journal-title":"Cell Rep"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0733-7","article-title":"Targeted therapy guided by single-cell transcriptomic analysis in drug-induced hypersensitivity syndrome: a case report","volume":"26","author":"Kim","year":"2020","journal-title":"Nat Med"},{"key":"B84","volume-title":"Cytomegaloviruses: Wolters Kluwer Health Adis (ESP)","author":"Mocarski","year":"2013"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00869","article-title":"Herpesvirus late gene expression: a viral-specific pre-initiation complex is key","volume":"7","author":"Gruffat","year":"2016","journal-title":"Front Microbiol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227919","article-title":"Decoding human cytomegalovirus","volume":"338","author":"Stern-Ginossar","year":"2012","journal-title":"Science"},{"key":"B87","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/s41587-021-01059-3","article-title":"Functional single-cell genomics of human cytomegalovirus infection","volume":"40","author":"Hein","year":"2022","journal-title":"Nat Biotechnol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02096","article-title":"Plasmacytoid DCs from patients with sjogren\u2019s syndrome are transcriptionally primed for enhanced pro-inflammatory cytokine production","volume":"10","author":"Hillen","year":"2019","journal-title":"Front Immunol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1016\/j.immuni.2018.04.015","article-title":"A single-cell transcriptomic atlas of thymus organogenesis resolves cell types and developmental maturation","volume":"48","author":"Kernfeld","year":"2018","journal-title":"Immunity"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02523","article-title":"Single-cell analysis identifies thymic maturation delay in growth-restricted neonatal mice","volume":"9","author":"Bacon","year":"2018","journal-title":"Front Immunol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3224","article-title":"A cell atlas of human thymic development defines T cell repertoire formation","volume":"367","author":"Park","year":"2020","journal-title":"Science"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/s41467-021-21346-6","article-title":"Single-cell transcriptional profiling of human thymic stroma uncovers novel cellular heterogeneity in the thymic medulla","volume":"12","author":"Bautista","year":"2021","journal-title":"Nat Commun"},{"key":"B93","doi-asserted-by":"publisher","first-page":"eade0182","DOI":"10.1126\/sciimmunol.ade0182","article-title":"Single-cell immune profiling reveals thymus-seeding populations, T cell commitment, and multilineage development in the human thymus","volume":"7","author":"Cordes","year":"2022","journal-title":"Sci Immunol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100506","article-title":"Single-cell transcriptomics reveals discrete steps in regulatory T cell development in the human thymus","volume":"208","author":"Morgana","year":"2022","journal-title":"J Immunol"},{"key":"B95","doi-asserted-by":"publisher","first-page":"5842","DOI":"10.1038\/s41467-022-33488-2","article-title":"Identification of distinct functional thymic programming of fetal and pediatric human gammadelta thymocytes via single-cell analysis","volume":"13","author":"Sanchez Sanchez","year":"2022","journal-title":"Nat Commun"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1202163","article-title":"Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis","volume":"14","author":"Farley","year":"2023","journal-title":"Front Immunol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01584-0","article-title":"Single-cell multiomic analysis of thymocyte development reveals drivers of CD4(+) T cell and CD8(+) T cell lineage commitment","volume":"24","author":"Steier","year":"2023","journal-title":"Nat Immunol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.035931","article-title":"MOHITO, a novel mouse cytokine-dependent T-cell line, enables studies of oncogenic signaling in the T-cell context","volume":"96","author":"Kleppe","year":"2011","journal-title":"Haematologica"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1995.1037","article-title":"Deficient antigen presentation by thymic epithelial cells reveals differential induction of T cell clone effector functions by CD28-mediated costimulation","volume":"161","author":"Lepesant","year":"1995","journal-title":"Cell Immunol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01663","article-title":"Cultured human thymic-derived cells display medullary thymic epithelial cell phenotype and functionality","volume":"9","author":"Villegas","year":"2018","journal-title":"Front Immunol"},{"key":"B101","first-page":"27","article-title":"Thymic epithelial cell culture","volume":"188","author":"Ropke","year":"2002","journal-title":"Methods Mol Biol"},{"key":"B102","doi-asserted-by":"publisher","first-page":"e15165","DOI":"10.1371\/journal.pone.0015165","article-title":"The PluriNetWork: an electronic representation of the network underlying pluripotency in mouse, and its applications","volume":"5","author":"Som","year":"2010","journal-title":"PloS One"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.03.030","article-title":"Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer\u2019s disease","volume":"153","author":"Zhang","year":"2013","journal-title":"Cell"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06816-9","article-title":"Dictionary of immune responses to cytokines at single-cell resolution","volume":"625","author":"Cui","year":"2023","journal-title":"Nature"},{"key":"B105","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1745-7580-5-5","article-title":"Ribosomal protein mRNAs are translationally-regulated during human dendritic cells activation by LPS","volume":"5","author":"Ceppi","year":"2009","journal-title":"Immunome Res"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0667-5","article-title":"NicheNet: modeling intercellular communication by linking ligands to target genes","volume":"17","author":"Browaeys","year":"2020","journal-title":"Nat Methods"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1813819115","article-title":"Virus-inclusive single-cell RNA sequencing reveals the molecular signature of progression to severe dengue","volume":"115","author":"Zanini","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.87696.3","article-title":"Rubella virus tropism and single-cell responses in human primary tissue and microglia-containing organoids","volume":"12","author":"Popova","year":"2023","journal-title":"Elife"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01405-y","article-title":"Modelling viral encephalitis caused by herpes simplex virus 1 infection in cerebral organoids","volume":"8","author":"Rybak-Wolf","year":"2023","journal-title":"Nat Microbiol"},{"key":"B110","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/329207a0","article-title":"HBLV (or HHV-6) in human cell lines","volume":"329","author":"Ablashi","year":"1987","journal-title":"Nature"},{"key":"B111","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/S0168-1702(96)01364-0","article-title":"Growth of human herpesvirus 6 in HEPG2 cells","volume":"45","author":"Cermelli","year":"1996","journal-title":"Virus Res"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.2.1173-1178.1994","article-title":"Human herpesvirus 6 infects cervical epithelial cells and transactivates human papillomavirus gene expression","volume":"68","author":"Chen","year":"1994","journal-title":"J Virol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.2.1296-1300.1996","article-title":"Infection of primary human fetal astrocytes by human herpesvirus 6","volume":"70","author":"He","year":"1996","journal-title":"J Virol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.11.7134","article-title":"TLR ligand-induced type I IFNs affect thymopoiesis","volume":"180","author":"Baron","year":"2008","journal-title":"J Immunol"},{"key":"B115","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.virol.2021.12.007","article-title":"Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection","volume":"567","author":"Demoulins","year":"2022","journal-title":"Virology"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203086","article-title":"IRF7-dependent IFN-beta production in response to RANKL promotes medullary thymic epithelial cell development","volume":"190","author":"Otero","year":"2013","journal-title":"J Immunol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500036","article-title":"IFN-alpha\/beta receptor signaling promotes regulatory T cell development and function under stress conditions","volume":"194","author":"Metidji","year":"2015","journal-title":"J Immunol"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3419","article-title":"Late stages of T cell maturation in the thymus involve NF-kappaB and tonic type I interferon signaling","volume":"17","author":"Xing","year":"2016","journal-title":"Nat Immunol"},{"key":"B119","doi-asserted-by":"publisher","first-page":"102389","DOI":"10.1016\/j.coi.2023.102389","article-title":"The role of interferon in the thymus","volume":"84","author":"Martinez","year":"2023","journal-title":"Curr Opin Immunol"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.5.3751-3759.1997","article-title":"Induction of T-cell apoptosis by human herpesvirus 6","volume":"71","author":"Inoue","year":"1997","journal-title":"J Virol"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-79-1-143","article-title":"Apoptosis of CD4+ T lymphocytes in human herpesvirus-6 infection","volume":"79","author":"Yasukawa","year":"1998","journal-title":"J Gen Virol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02532","article-title":"Biology of IL-36 signaling and its role in systemic inflammatory diseases","volume":"10","author":"Yuan","year":"2019","journal-title":"Front Immunol"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.621931","article-title":"Interleukin-1 as innate mediator of T cell immunity","volume":"11","author":"Van Den Eeckhout","year":"2020","journal-title":"Front Immunol"},{"key":"B124","doi-asserted-by":"publisher","first-page":"4700","DOI":"10.1038\/s41467-019-12318-y","article-title":"IL-36 promotes anti-viral immunity by boosting sensitivity to IFN-alpha\/beta in IRF1 dependent and independent manners","volume":"10","author":"Wang","year":"2019","journal-title":"Nat Commun"},{"key":"B125","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.immuni.2005.11.012","article-title":"Developmental and molecular characterization of emerging beta- and gammadelta-selected pre-T cells in the adult mouse thymus","volume":"24","author":"Taghon","year":"2006","journal-title":"Immunity"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01664","article-title":"Cholesterol metabolism in T cells","volume":"8","author":"Bietz","year":"2017","journal-title":"Front Immunol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1084\/jem.120.5.857","article-title":"Virus particles in the thymus of conventional and germ-free mice","volume":"120","author":"Deharven","year":"1964","journal-title":"J Exp Med"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2022.03.008","article-title":"Negative times negative equals positive, THEMIS sets the rule on thymic selection and peripheral T cell responses","volume":"45","author":"Melique","year":"2022","journal-title":"BioMed J"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-111315-125324","article-title":"TCR signal strength and T cell development","volume":"32","author":"Gascoigne","year":"2016","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.4.471","article-title":"The role of recombination activating gene (RAG) reinduction in thymocyte development in vivo","volume":"194","author":"Yannoutsos","year":"2001","journal-title":"J Exp Med"},{"key":"B131","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1126\/science.1188989","article-title":"An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b","volume":"329","author":"Li","year":"2010","journal-title":"Science"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.11.5668","article-title":"Down-regulation of the orphan nuclear receptor ROR gamma t is essential for T lymphocyte maturation","volume":"164","author":"He","year":"2000","journal-title":"J Immunol"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1766","article-title":"Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling","volume":"10","author":"Fu","year":"2009","journal-title":"Nat Immunol"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1769","article-title":"Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection","volume":"10","author":"Johnson","year":"2009","journal-title":"Nat Immunol"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1768","article-title":"Themis, a T cell-specific protein important for late thymocyte development","volume":"10","author":"Lesourne","year":"2009","journal-title":"Nat Immunol"},{"key":"B136","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.jaut.2013.12.016","article-title":"Central role of interferon-beta in thymic events leading to myasthenia gravis","volume":"52","author":"Cufi","year":"2014","journal-title":"J Autoimmun"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.06.015","article-title":"The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance","volume":"29","author":"Akiyama","year":"2008","journal-title":"Immunity"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302550","article-title":"Thymic medullary epithelium and thymocyte self-tolerance require cooperation between CD28-CD80\/86 and CD40-CD40L costimulatory pathways","volume":"192","author":"Williams","year":"2014","journal-title":"J Immunol"},{"key":"B139","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.it.2017.10.007","article-title":"Chemokine-mediated choreography of thymocyte development and selection","volume":"39","author":"Lancaster","year":"2018","journal-title":"Trends Immunol"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05438.x","article-title":"The thymus at the crossroad of neuroimmune interactions","volume":"917","author":"Maroder","year":"2000","journal-title":"Ann N Y Acad Sci"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.7150\/jca.28231","article-title":"The expression, functions, interactions and prognostic values of PTPRZ1: A review and bioinformatic analysis","volume":"10","author":"Xia","year":"2019","journal-title":"J Cancer"},{"key":"B142","doi-asserted-by":"publisher","first-page":"e103405","DOI":"10.1371\/journal.pone.0103405","article-title":"Semaphorin 3F and neuropilin-2 control the migration of human T-cell precursors","volume":"9","author":"Mendes-da-Cruz","year":"2014","journal-title":"PloS One"},{"key":"B143","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/msb.2012.56","article-title":"PLAU inferred from a correlation network is critical for suppressor function of regulatory T cells","volume":"8","author":"He","year":"2012","journal-title":"Mol Syst Biol"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1080\/19336918.2017.1327513","article-title":"Small interference ITGA6 gene targeting in the human thymic epithelium differentially regulates the expression of immunological synapse-related genes","volume":"12","author":"Golbert","year":"2018","journal-title":"Cell Adh Migr"},{"key":"B145","doi-asserted-by":"publisher","first-page":"2842","DOI":"10.1038\/ncomms3842","article-title":"Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output","volume":"4","author":"Emre","year":"2013","journal-title":"Nat Commun"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710522114","article-title":"Transcriptome-wide characterization of human cytomegalovirus in natural infection and experimental latency","volume":"114","author":"Cheng","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.692515","article-title":"Human cytomegalovirus UL23 attenuates signal transducer and activator of transcription 1 phosphorylation and type I interferon response","volume":"12","author":"Feng","year":"2021","journal-title":"Front Microbiol"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-6-1315","article-title":"The products of human cytomegalovirus genes UL23, UL24, UL43 and US22 are tegument components","volume":"83","author":"Adair","year":"2002","journal-title":"J Gen Virol"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-009-0420-y","article-title":"The conserved UL24 family of human alpha, beta and gamma herpesviruses induces cell cycle arrest and inactivation of the cyclinB\/cdc2 complex","volume":"154","author":"Nascimento","year":"2009","journal-title":"Arch Virol"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1268429","article-title":"Mechanism of herpesvirus UL24 protein regulating viral immune escape and virulence","volume":"14","author":"Ruan","year":"2023","journal-title":"Front Microbiol"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01419-18","article-title":"RNA sequencing of the in vivo human herpesvirus 6B transcriptome to identify targets for clinical assays distinguishing between latent and active infections","volume":"93","author":"Hill","year":"2019","journal-title":"J Virol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1375508\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T10:01:29Z","timestamp":1721383289000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1375508\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,4]]},"references-count":151,"alternative-id":["10.3389\/fimmu.2024.1375508"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1375508","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,4]]},"article-number":"1375508"}}