{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:29:58Z","timestamp":1790512198600,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010152","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000}}],"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T00:00:00Z","timestamp":1639612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["ALWOP.512"],"award-info":[{"award-number":["ALWOP.512"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007192","name":"Rijksinstituut voor Volksgezondheid en Milieu","doi-asserted-by":"publisher","award":["Strategic Program Research"],"award-info":[{"award-number":["Strategic Program Research"]}],"id":[{"id":"10.13039\/501100007192","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Cytomegalovirus (CMV) infection has a major impact on the T-cell pool, which is thought to be associated with ageing of the immune system. The effect on the T-cell pool has been interpreted as an effect of CMV on non-CMV specific T-cells. However, it remains unclear whether the effect of CMV could simply be explained by the presence of large, immunodominant, CMV-specific memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell populations. These have been suggested to establish through gradual accumulation of long-lived cells. However, little is known about their maintenance. We investigated the effect of CMV infection on T-cell dynamics in healthy older adults, and aimed to unravel the mechanisms of maintenance of large numbers of CMV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells. We studied the expression of senescence, proliferation, and apoptosis markers and quantified the\n                    <jats:italic>in vivo<\/jats:italic>\n                    dynamics of CMV-specific and other memory T-cell populations using\n                    <jats:italic>in vivo<\/jats:italic>\n                    deuterium labelling. Increased expression of late-stage differentiation markers by CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells of CMV+ versus CMV- individuals was not solely explained by the presence of large, immunodominant CMV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell populations. The lifespans of circulating CMV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells did not differ significantly from those of bulk memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells, and the lifespans of bulk memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells did not differ significantly between CMV- and CMV+ individuals. Memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cells of CMV+ individuals showed increased expression of late-stage differentiation markers and decreased Ki-67 expression. Overall, the expression of senescence markers on T-cell populations correlated positively with their expected\n                    <jats:italic>in vivo<\/jats:italic>\n                    lifespan. Together, this work suggests that i) large, immunodominant CMV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell populations do not explain the phenotypical differences between CMV+ and CMV- individuals, ii) CMV infection hardly affects the dynamics of the T-cell pool, and iii) large numbers of CMV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells are not due to longer lifespans of these cells.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010152","type":"journal-article","created":{"date-parts":[[2021,12,16]],"date-time":"2021-12-16T13:53:00Z","timestamp":1639662780000},"page":"e1010152","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":45,"title":["Quantification of T-cell dynamics during latent cytomegalovirus infection in humans"],"prefix":"10.1371","volume":"17","author":[{"given":"Sara P. H.","family":"van den Berg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6345-2678","authenticated-orcid":true,"given":"Lyanne Y.","family":"Derksen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9434-8459","authenticated-orcid":true,"given":"Julia","family":"Drylewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nening M.","family":"Nanlohy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4875-312X","authenticated-orcid":true,"given":"Lisa","family":"Beckers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josien","family":"Lanfermeijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie N.","family":"Gessel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7175-625X","authenticated-orcid":true,"given":"Martijn","family":"Vos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid A.","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-691X","authenticated-orcid":true,"given":"Rob J.","family":"de Boer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiki","family":"Tesselaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2931-0390","authenticated-orcid":true,"given":"Jos\u00e9 A. M.","family":"Borghans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"van Baarle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"issue":"1","key":"ppat.1010152.ref001","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.virusres.2006.01.002","article-title":"Topics in herpesvirus genomics and evolution","volume":"117","author":"DJ McGeoch","year":"2006","journal-title":"Virus Res"},{"issue":"5","key":"ppat.1010152.ref002","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.4049\/jimmunol.1301721","article-title":"Aging and Cytomegalovirus Infection Differentially and Jointly Affect Distinct Circulating T Cell Subsets in Humans","volume":"192","author":"AM Wertheimer","year":"2014","journal-title":"J Immunol"},{"key":"ppat.1010152.ref003","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2017.00733","article-title":"Latent cytomegalovirus (CMV) infection does not detrimentally alter T cell responses in the healthy old, but increased latent CMV carriage is related to expanded CMV-specific T cells","volume":"8","author":"SE Jackson","year":"2017","journal-title":"Front Immunol"},{"key":"ppat.1010152.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep26892","article-title":"Differential effects of Cytomegalovirus carriage on the immune phenotype of middle-aged males and females","volume":"6","author":"M Van der Heiden","year":"2016","journal-title":"Sci Rep"},{"issue":"12","key":"ppat.1010152.ref005","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1099\/vir.0.036004-0","article-title":"Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of latedifferentiated CD4+ and CD8+ T-cells in humans","volume":"92","author":"E Derhovanessian","year":"2011","journal-title":"J Gen Virol"},{"key":"ppat.1010152.ref006","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4933-9-23","article-title":"CMV and Immunosenescence: From basics to clinics","volume":"9","author":"R Solana","year":"2012","journal-title":"Immun Ageing."},{"key":"ppat.1010152.ref007","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4933-8-10","article-title":"Report from the second cytomegalovirus and immunosenescence workshop","volume":"8","author":"M Wills","year":"2011","journal-title":"Immun Ageing"},{"issue":"5","key":"ppat.1010152.ref008","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1084\/jem.20050882","article-title":"Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects","volume":"202","author":"AW Sylwester","year":"2005","journal-title":"J Exp Med"},{"issue":"3\u20134","key":"ppat.1010152.ref009","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s00430-019-00608-7","article-title":"The hallmarks of CMV-specific CD8 T-cell differentiation","volume":"208","author":"SPH Van den Berg","year":"2019","journal-title":"Med Microbiol Immunol"},{"issue":"3\u20134","key":"ppat.1010152.ref010","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s00430-019-00607-8","article-title":"Cytomegalovirus memory inflation and immune protection","volume":"208","author":"L. Cicin-Sain","year":"2019","journal-title":"Med Microbiol Immunol"},{"issue":"24","key":"ppat.1010152.ref011","doi-asserted-by":"crossref","first-page":"11495","DOI":"10.1128\/JVI.74.24.11495-11503.2000","article-title":"Enrichment of Immediate-Early 1 (m123\/pp89) Peptide-Specific CD8 T Cells in a Pulmonary CD62Llo Memory-Effector Cell Pool during Latent Murine Cytomegalovirus Infection of the Lungs","volume":"74","author":"R Holtappels","year":"2000","journal-title":"J Virol"},{"issue":"4","key":"ppat.1010152.ref012","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.4049\/jimmunol.170.4.2022","article-title":"Memory Inflation: Continuous Accumulation of Antiviral CD8+ T Cells Over Time","volume":"170","author":"U Karrer","year":"2003","journal-title":"J Immunol"},{"issue":"1","key":"ppat.1010152.ref013","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/imr.12653","article-title":"The (gradual) rise of memory inflation","volume":"283","author":"P Klenerman","year":"2018","journal-title":"Immunol Rev"},{"issue":"3\u20134","key":"ppat.1010152.ref014","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00430-019-00587-9","article-title":"Fuel and brake of memory T cell inflation","volume":"208","author":"SPM Welten","year":"2019","journal-title":"Med Microbiol Immunol"},{"issue":"3","key":"ppat.1010152.ref015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/vaccines8030402","article-title":"Revisiting CD8 T-cell \u2018memory inflation\u2019: New insights with implications for cytomegaloviruses as vaccine vectors.","volume":"8","author":"R Holtappels","year":"2020","journal-title":"Vaccines"},{"key":"ppat.1010152.ref016","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2017.01776","article-title":"Cytomegalovirus-specific T cells restricted by HLA-Cw*0702 increase markedly with age and dominate the CD8+ T-cell repertoire in older people.","volume":"8","author":"L Hosie","year":"2017","journal-title":"Front Immunol"},{"issue":"6","key":"ppat.1010152.ref017","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nri.2016.38","article-title":"T cell responses to cytomegalovirus","volume":"16","author":"P Klenerman","year":"2016","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"ppat.1010152.ref018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0151965","article-title":"Impact of persistent cytomegalovirus infection on dynamic changes in human immune system profile","volume":"11","author":"R Vescovini","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"ppat.1010152.ref019","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1365-2567.2010.03334.x","article-title":"Human cytomegalovirus-specific CD8+ T-cell expansions contain long-lived cells that retain functional capacity in both young and elderly subjects","volume":"132","author":"DL Wallace","year":"2011","journal-title":"Immunology"},{"issue":"2","key":"ppat.1010152.ref020","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/acel.12311","article-title":"Lymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover","volume":"14","author":"L Westera","year":"2015","journal-title":"Aging Cell"},{"issue":"3","key":"ppat.1010152.ref021","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s11357-012-9381-2","article-title":"The role of the T cell in age-related inflammation","volume":"35","author":"R Macaulay","year":"2013","journal-title":"Age (Omaha)."},{"issue":"4","key":"ppat.1010152.ref022","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.immuni.2008.07.017","article-title":"Memory Inflation during Chronic Viral Infection Is Maintained by Continuous Production of Short-Lived, Functional T Cells","volume":"29","author":"CM Snyder","year":"2008","journal-title":"Immunity"},{"issue":"5","key":"ppat.1010152.ref023","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s10522-015-9563-2","article-title":"Impact of age, sex and CMV-infection on peripheral T cell phenotypes: results from the Berlin BASE-II Study","volume":"16","author":"S Di Benedetto","year":"2015","journal-title":"Biogerontology"},{"issue":"2","key":"ppat.1010152.ref024","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1006\/clim.1998.4638","article-title":"Role of cytomegalovirus in the T cell changes seen in elderly individuals","volume":"90","author":"RJ Looney","year":"1999","journal-title":"Clin Immunol"},{"issue":"6","key":"ppat.1010152.ref025","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2174\/157016210793499268","article-title":"High levels of CD57+CD28- T-cells, low T-cell proliferation and preferential expansion of terminally differentiated CD4+ T-cells in HIV-elite controllers","volume":"8","author":"E Ruiz-Mateos","year":"2010","journal-title":"Curr HIV Res"},{"issue":"1","key":"ppat.1010152.ref026","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1365-2567.2011.03470.x","article-title":"CD8+CD28- and CD8+CD57+ T cells and their role in health and disease","volume":"134","author":"M Strioga","year":"2011","journal-title":"Immunology"},{"issue":"12","key":"ppat.1010152.ref027","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.1038\/nprot.2007.420","article-title":"Measurement of cell proliferation by heavy water labeling","volume":"2","author":"R Busch","year":"2007","journal-title":"Nat Protoc"},{"issue":"11","key":"ppat.1010152.ref028","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1016\/j.celrep.2016.11.037","article-title":"Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux","volume":"17","author":"R Ahmed","year":"2016","journal-title":"Cell Rep"},{"key":"ppat.1010152.ref029","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fragi.2021.665637","article-title":"Age and CMV-Infection Jointly Affect the EBV-Specific CD8+ T-Cell Repertoire","volume":"2","author":"J Lanfermeijer","year":"2021","journal-title":"Front Aging"},{"key":"ppat.1010152.ref030","first-page":"1","article-title":"Cytotoxic CD4 T cells-friend or foe during viral infection?","volume":"8","author":"JA Juno","year":"2017","journal-title":"Front Immunol"},{"issue":"16","key":"ppat.1010152.ref031","doi-asserted-by":"crossref","first-page":"4509","DOI":"10.7150\/thno.27428","article-title":"CD28null pro-atherogenic CD4 T-cells explain the link between CMV infection and an increased risk of cardiovascular death","volume":"8","author":"A Pera","year":"2018","journal-title":"Theranostics"},{"issue":"7685","key":"ppat.1010152.ref032","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nature24633","article-title":"Origin and differentiation of human memory CD8 T cells after vaccination","volume":"552","author":"RS Akondy","year":"2017","journal-title":"Nature"},{"issue":"4","key":"ppat.1010152.ref033","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.coi.2009.05.012","article-title":"Biomarkers of human immunosenescence: impact of Cytomegalovirus infection","volume":"21","author":"E Derhovanessian","year":"2009","journal-title":"Curr Opin Immunol"},{"key":"ppat.1010152.ref034","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.0105-2896.2005.00271.x","article-title":"Human immunosenescence: Is it infectious?","volume":"205","author":"G Pawelec","year":"2005","journal-title":"Immunol Rev"},{"key":"ppat.1010152.ref035","first-page":"1","article-title":"Mechanisms underlying T cell immunosenescence: Aging and cytomegalovirus infection","volume":"7","author":"W Tu","year":"2016","journal-title":"Front Microbiol"},{"key":"ppat.1010152.ref036","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/rmv.1862","article-title":"Cytomegalovirus latency and reactivation: recent insights into an age old problem","volume":"26","author":"L Dupont","year":"2016","journal-title":"Rev Med Virol"},{"issue":"6","key":"ppat.1010152.ref037","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.exger.2007.01.005","article-title":"Chronic herpesvirus reactivation occurs in aging","volume":"42","author":"RP Stowe","year":"2007","journal-title":"Exp Gerontol"},{"issue":"9","key":"ppat.1010152.ref038","doi-asserted-by":"crossref","first-page":"e1005719","DOI":"10.1371\/journal.pcbi.1005719","article-title":"Infectious Reactivation of Cytomegalovirus Explaining Age- And Sex-Specific Patterns of Seroprevalence.","volume":"13","author":"M van Boven","year":"2017","journal-title":"PLoS Comput Biol"},{"issue":"13","key":"ppat.1010152.ref039","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1182\/blood-2013-03-488411","article-title":"Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans","volume":"122","author":"L Westera","year":"2013","journal-title":"Blood"},{"key":"ppat.1010152.ref040","article-title":"Turnover of MCMV-expanded CD8+ T-cells is similar to that of memory phenotype T-cells and independent of the magnitude of the response","author":"M Baliu-Piqu\u00e9","year":"2021","journal-title":"bioRxiv"},{"issue":"10","key":"ppat.1010152.ref041","doi-asserted-by":"crossref","first-page":"e1193","DOI":"10.1002\/cti2.1193","article-title":"Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27-year-long longitudinal study","volume":"9","author":"LD Samson","year":"2020","journal-title":"Clin Transl Immunol"},{"issue":"1","key":"ppat.1010152.ref042","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3390\/vaccines5010005","article-title":"Human T cell memory: A dynamic view","volume":"5","author":"DC Macallan","year":"2017","journal-title":"Vaccines"},{"issue":"12","key":"ppat.1010152.ref043","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/S1471-4906(02)02337-2","article-title":"Lymphocyte kinetics: The interpretation of labelling data","volume":"23","author":"B Asquith","year":"2002","journal-title":"Trends Immunol"},{"issue":"2","key":"ppat.1010152.ref044","doi-asserted-by":"crossref","first-page":"e1000666","DOI":"10.1371\/journal.pcbi.1000666","article-title":"Explicit kinetic heterogeneity: Mathematical models for interpretation of deuterium labeling of heterogeneous cell populations","volume":"6","author":"VV Ganusov","year":"2010","journal-title":"PLoS Comput Biol"},{"issue":"7","key":"ppat.1010152.ref045","doi-asserted-by":"crossref","first-page":"3759","DOI":"10.4049\/jimmunol.1100666","article-title":"Functional CD8 T Cell Memory Responding to Persistent Latent Infection Is Maintained for Life","volume":"187","author":"A Lang","year":"2011","journal-title":"J Immunol"},{"issue":"1\u20133","key":"ppat.1010152.ref046","first-page":"187","article-title":"Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study","volume":"121","author":"J Olsson","year":"2000","journal-title":"Mech Ageing Dev"},{"key":"ppat.1010152.ref047","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exger.2013.11.010","article-title":"Immunosenenescence: Role of cytomegalovirus","volume":"54","author":"G. Pawelec","year":"2014","journal-title":"Exp Gerontol"},{"key":"ppat.1010152.ref048","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0531-5565(01)00212-1","article-title":"Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study","volume":"37","author":"A Wikby","year":"2002","journal-title":"Exp Gerontol"},{"key":"ppat.1010152.ref049","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jim.2018.07.003","article-title":"The development of a bead-based multiplex immunoassay for the detection of IgG antibodies to CMV and EBV","volume":"462","author":"I Tcherniaeva","year":"2018","journal-title":"J Immunol Methods"},{"issue":"6","key":"ppat.1010152.ref050","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/S0026-0495(98)90035-X","article-title":"Improved accuracy and precision of gas chromatography\/mass spectrometry measurements for metabolic tracers","volume":"47","author":"BW Patterson","year":"1998","journal-title":"Metabolism"},{"issue":"10","key":"ppat.1010152.ref051","doi-asserted-by":"crossref","first-page":"e1004355","DOI":"10.1371\/journal.pcbi.1004355","article-title":"Reconciling Estimates of Cell Proliferation from Stable Isotope Labeling Experiments","volume":"11","author":"R Ahmed","year":"2015","journal-title":"PLoS Comput Biol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010152","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010152","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T13:34:43Z","timestamp":1640871283000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010152"}},"subtitle":[],"editor":[{"given":"Laurent","family":"Coscoy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,12,16]]},"references-count":51,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010152","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,16]]}}}