{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:26:10Z","timestamp":1793370370678,"version":"4.5.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"17","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Chronic infections with viruses such as hepatitis B virus, hepatitis C virus, and HIV constitute a major global public health problem. Studies of chronic viral infections in humans and mice show that persistent antigenic stimulation induces dysregulation of T cell responses; virus-specific T cells either undergo clonal deletion or lose their ability to display the full spectrum of effector functions, a condition termed functional exhaustion. The ability to generate and retain sufficient numbers of functionally competent T cells, therefore, becomes vitally important in controlling chronic viral infections. Our understanding of the mechanisms governing T cell homeostasis during chronic viral infections, however, is poor. The phosphatidylinositol 3-kinase (PI3K)\/Akt signaling pathway controls cell fate decisions in many cell types by modulating the activity of downstream effectors, including the FOXO family of transcription factors. We have observed dynamic,\n            <jats:italic>in vivo<\/jats:italic>\n            alterations in the phosphorylation levels of three key proteins (Akt, FOXO1\/FOXO3 [FOXO1\/3], and mammalian target of rapamycin [mTOR]) involved in this signaling cascade and have identified the transcription factor FOXO3 as a negative regulator of the magnitude and effector function of CD8 T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. We report that ablation of FOXO3 in T cells reduced apoptosis, increased the abundance of polyfunctional virus-specific CD8 T cells, and improved viral control. Thus, FOXO3 is a promising candidate target for immunotherapies of chronic viral infection.\n          <\/jats:p>","DOI":"10.1128\/jvi.00942-12","type":"journal-article","created":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T01:11:02Z","timestamp":1339031462000},"page":"9025-9034","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["FOXO3 Regulates the CD8 T Cell Response to a Chronic Viral Infection"],"prefix":"10.1128","volume":"86","author":[{"given":"Jeremy A.","family":"Sullivan","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eui Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin H.","family":"Plisch","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.8.4242-4247.1991"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.521"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070784"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni804"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040789"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.4.1623"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1679"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2005.01.004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80388-X"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.21"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838336"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.5.2730"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1729"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00728-4"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.5.2980"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.07034-11"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00855-06"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705007104"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1784"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1689"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1241"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100102"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0703-861"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168676"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2008.35"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1042\/bst0320360"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.12.8056-8063.1994"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/362758a0"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80470-7"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-323154"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100038"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01350-07"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.02.003"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283377a1e"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.12.029"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0804-806"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.01.011"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.26"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1080\/08916930701464913"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1573"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061681"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-160945"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071641"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.06.004"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.10.5024"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002533"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.8.3906-3918.2004"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.06.015"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.01.003"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1482"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1728"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.06.036"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20102516"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.8.4911-4927.2003"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070618"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060353"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.12.2205"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.2.829-840.2002"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00942-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00942-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T15:14:31Z","timestamp":1646493271000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00942-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9]]},"references-count":60,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2012,9]]}},"alternative-id":["10.1128\/JVI.00942-12"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00942-12","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9]]},"assertion":[{"value":"2012-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-05-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}