{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:33:12Z","timestamp":1784806392664,"version":"3.55.0"},"reference-count":73,"publisher":"National Academy of Sciences","issue":"38","license":[{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI116158"],"award-info":[{"award-number":["AI116158"]}],"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":["AI148383"],"award-info":[{"award-number":["AI148383"]}],"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":["AI131957"],"award-info":[{"award-number":["AI131957"]}],"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":["AI120691"],"award-info":[{"award-number":["AI120691"]}],"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":["AI150476"],"award-info":[{"award-number":["AI150476"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM007315"],"award-info":[{"award-number":["GM007315"]}],"id":[{"id":"10.13039\/100000057","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":["AI007413"],"award-info":[{"award-number":["AI007413"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM008353"],"award-info":[{"award-number":["GM008353"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,9,22]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>This study describes the discovery of a class of drug that can help the immune system eliminate hard-to-kill cells infected with HIV. HIV establishes a persistent infection for which there is no cure, necessitating the development of new approaches to enhance the clearance of HIV-infected cells. HIV encodes Nef, which down-regulates MHC-I expression in infected cells to impair immune-mediated clearance by cytotoxic T lymphocytes. We identified the plecomacrolide family of natural products as potent inhibitors of Nef, and concanamycin A restored MHC-I and enhanced the clearance of HIV-infected primary cells by cytotoxic T lymphocytes. Concanamycin A counteracted Nef from diverse clades of HIV targeting multiple allotypes of MHC-I, indicating the potential for broad therapeutic utility.<\/jats:p>","DOI":"10.1073\/pnas.2008615117","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T15:57:19Z","timestamp":1599580639000},"page":"23835-23846","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":19,"title":["Concanamycin A counteracts HIV-1 Nef to enhance immune clearance of infected primary cells by cytotoxic T lymphocytes"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0180-2748","authenticated-orcid":false,"given":"Mark M.","family":"Painter","sequence":"first","affiliation":[{"name":"Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen E.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline S.","family":"Merlino","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Natural Products Discovery Core, Life Sciences Institute, University of Michigan Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2499-3882","authenticated-orcid":false,"given":"Valeri H.","family":"Terry","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;"},{"name":"California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan R.","family":"McLeod","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyanne","family":"Gomez-Rodriguez","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Graduate Program in Chemical Biology, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolie A.","family":"Leonard","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay E.","family":"Leopold","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Neevel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7125-453X","authenticated-orcid":false,"given":"Jay","family":"Lubow","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Olson","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Piechocka-Trocha","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 20815;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Collins","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 20815;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashootosh","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Natural Products Discovery Core, Life Sciences Institute, University of Michigan Ann Arbor, MI 48109;"},{"name":"Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1345-9318","authenticated-orcid":false,"given":"Malini","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6122-9245","authenticated-orcid":false,"given":"Bruce D.","family":"Walker","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;"},{"name":"Howard Hughes Medical Institute, Chevy Chase, MD 20815;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5054-5445","authenticated-orcid":false,"given":"James H.","family":"Hurley","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;"},{"name":"California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-3647","authenticated-orcid":false,"given":"David H.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Department of Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen L.","family":"Collins","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109;"},{"name":"Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,9,8]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-205"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.08.012"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni845"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611244104"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav5095"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67098-5"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.01.014"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11286"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14053"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI97555"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/370650a0"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1161"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1570"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2010.00893.x"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5258.67"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1195271"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0496-405"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2009.00979.x"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200407031"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707760200"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00056-11"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000131"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm729"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2328"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac5137"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01322-19"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/34929"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80065-5"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.23.12173-12184.2002"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.11.019"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.5.3041-3049.2003"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(01)00298-1"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/tan.12095"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057112450186"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3597"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2012.11.005"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93684"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02151"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.200.1.1"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.37.1333"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2009.08.003"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1006\/cbir.1994.1060"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041570303"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-018-0066-7"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.02014"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604143200"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.5.3157"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80483-5"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2015.08.010"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/352067a0"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/375148a0"},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.4049\/jimmunol.156.10.3678","article-title":"Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity","volume":"156","author":"Kataoka T.","year":"1996","unstructured":"T. Kataoka ., Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity. J. Immunol. 156, 3678\u20133686 (1996).","journal-title":"J. Immunol."},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(97)02698-9"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03113"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403234"},{"key":"e_1_3_4_56_2","first-page":"e01409","article-title":"Resistance of major histocompatibility complex class B (MHC-B) to Nef-mediated downregulation relative to that of MHC-A is conserved among primate lentiviruses and influences antiviral T cell responses in HIV-1-infected individuals","volume":"92","author":"Mwimanzi F.","year":"2017","unstructured":"F. Mwimanzi ., Resistance of major histocompatibility complex class B (MHC-B) to Nef-mediated downregulation relative to that of MHC-A is conserved among primate lentiviruses and influences antiviral T cell responses in HIV-1-infected individuals. J. Virol. 92, e01409-17 (2017).","journal-title":"J. Virol."},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34961"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.11.104"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00229-11"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00196-18"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.3.1527-1534.1996"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054295"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-018-0388-3"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.4.12.1251"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.03.015"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200522200"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80569-5"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.2.463"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01845-19"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI132374"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.10.014"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2008.11.021"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02110-17"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2008615117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2008615117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T21:44:07Z","timestamp":1696628647000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2008615117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,8]]},"references-count":73,"journal-issue":{"issue":"38","published-print":{"date-parts":[[2020,9,22]]}},"alternative-id":["10.1073\/pnas.2008615117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2008615117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,8]]},"assertion":[{"value":"2020-09-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}