{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:20:50Z","timestamp":1788448850568,"version":"build-2803163510"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"22","license":[{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"VA Merit Review Award","award":["1I01BX004281"],"award-info":[{"award-number":["1I01BX004281"]}]},{"name":"DoD Award","award":["PR170067"],"award-info":[{"award-number":["PR170067"]}]},{"name":"VA Merit Review Award","award":["1I01BX002670"],"award-info":[{"award-number":["1I01BX002670"]}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI114748"],"award-info":[{"award-number":["R01AI114748"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI138598"],"award-info":[{"award-number":["R21AI138598"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2020,10,27]]},"abstract":"<jats:p>The hallmark of HIV infection is a gradual depletion of CD4 T cells, with a progressive decline of host immunity. How CD4 T cells are depleted in individuals with active and virus-suppressed HIV infection remains unclear. In this study, we employed a cellular model of HIV infection to characterize the mechanisms underlying CD4 T-cell destruction by analyzing the chromosome end (telomere) DNA damage response (DDR) and cellular apoptosis in a T-cell line (highly permissive SupT1 cells), as well as in primary CD4 T cells with active or drug-suppressed HIV infection. We demonstrated that HIV-induced telomeric DDR plays a critical role in inducing telomere loss, premature cell aging, and CD4 T-cell apoptosis or depletion via dysregulation of the PI3K\/ATM pathways. This study sheds new light on the molecular mechanisms of telomeric DDR and its role in CD4 T-cell homeostasis during HIV infection.<\/jats:p>","DOI":"10.1128\/jvi.01061-20","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T13:22:00Z","timestamp":1599484920000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Telomere and ATM Dynamics in CD4 T-Cell Depletion in Active and Virus-Suppressed HIV Infections"],"prefix":"10.1128","volume":"94","author":[{"given":"Sushant","family":"Khanal","sequence":"first","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyuan","family":"Tang","sequence":"additional","affiliation":[{"name":"The Third People\u2019s Hospital, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechao","family":"Cao","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam Nhat","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwayomi Samson","family":"Oyedeji","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xindi","family":"Dang","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam Ngoc Thao","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Schank","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal Krishna Chand","family":"Thakuri","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinyere","family":"Ogbu","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng D.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao Y.","family":"Wu","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Third People\u2019s Hospital, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"He","sequence":"additional","affiliation":[{"name":"The Third People\u2019s Hospital, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El Gazzar","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengke","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunbin","family":"Ning","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Moorman","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"},{"name":"Hepatitis (HCV\/HBV\/HIV) Program, James H. Quillen VA Medical Center, Department of Veterans Affairs, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-1007","authenticated-orcid":false,"given":"Zhi Q.","family":"Yao","sequence":"additional","affiliation":[{"name":"Center of Excellence in Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA"},{"name":"Department of Internal Medicine, Division of Infectious, Inflammatory and Immunologic Diseases, Quillen College of Medicine, ETSU, Johnson City, Tennessee, USA"},{"name":"Hepatitis (HCV\/HBV\/HIV) Program, James H. Quillen VA Medical Center, Department of Veterans Affairs, Johnson City, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12066"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00580"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000448542"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2016.1195536"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2017.04.002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2017.07.007"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw146"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0000000000000398"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/429298"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/375841"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033488"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.04.049"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.03.018"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/653707"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.025130"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1006-1133"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/35040500"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtbi.2004.12.016"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0897-y"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-018-0015-4"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01152"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02531"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-019-0153-z"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2395-2"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006866"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.59.2.284-291.1986"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030176"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005931"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2015.0106"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005006"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.4.2196"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811332106"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2115"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/em.21944"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00542-6"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2007.02.009"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb1090"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.169730"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.22932"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-018-0391-8"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01606"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2014.06.009"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0512-555b"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1009-1272a"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00795.x"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2017.1312225"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2018.1520568"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01061-20","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01061-20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T15:00:49Z","timestamp":1646492449000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01061-20"}},"subtitle":[],"editor":[{"given":"Viviana","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,10,27]]},"references-count":47,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2020,10,27]]}},"alternative-id":["10.1128\/JVI.01061-20"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01061-20","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,27]]},"assertion":[{"value":"2020-05-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01061-20"}}