{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:59:56Z","timestamp":1792735196832,"version":"4.5.0"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"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":[[2013,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Cytotoxic-T-lymphocyte (CTL) escape mutations undermine the durability of effective human immunodeficiency virus type 1 (HIV-1)-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cell responses. The rate of CTL escape from a given response is largely governed by the net of all escape-associated viral fitness costs and benefits. The observation that CTL escape mutations can carry an associated fitness cost in terms of reduced virus replication capacity (RC) suggests a fitness cost-benefit trade-off that could delay CTL escape and thereby prolong CD8 response effectiveness. However, our understanding of this potential fitness trade-off is limited by the small number of CTL escape mutations for which a fitness cost has been quantified. Here, we quantified the fitness cost of the 29 most common HIV-1B Gag CTL escape mutations using an\n            <jats:italic>in vitro<\/jats:italic>\n            RC assay. The majority (20\/29) of mutations reduced RC by more than the benchmark M184V antiretroviral drug resistance mutation, with impacts ranging from 8% to 69%. Notably, the reduction in RC was significantly greater for CTL escape mutations associated with protective HLA class I alleles than for those associated with nonprotective alleles. To speed the future evaluation of CTL escape costs, we also developed an\n            <jats:italic>in silico<\/jats:italic>\n            approach for inferring the relative impact of a mutation on RC based on its computed impact on protein thermodynamic stability. These data illustrate that the magnitude of CTL escape-associated fitness costs, and thus the barrier to CTL escape, varies widely even in the conserved Gag proteins and suggest that differential escape costs may contribute to the relative efficacy of CD8 responses.\n          <\/jats:p>","DOI":"10.1128\/jvi.03233-12","type":"journal-article","created":{"date-parts":[[2013,1,31]],"date-time":"2013-01-31T05:06:58Z","timestamp":1359608818000},"page":"3952-3965","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":45,"title":["Frequent and Variable Cytotoxic-T-Lymphocyte Escape-Associated Fitness Costs in the Human Immunodeficiency Virus Type 1 Subtype B Gag Proteins"],"prefix":"10.1128","volume":"87","author":[{"given":"Christian L.","family":"Boutwell","sequence":"first","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Microsoft Research, eScience Group, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Ho","family":"Lin","sequence":"additional","affiliation":[{"name":"Microsoft Research, eScience Group, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Seese","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen A.","family":"Power","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Peng","sequence":"additional","affiliation":[{"name":"Microsoft Research, eScience Group, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Tang","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zabrina L.","family":"Brumme","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada"},{"name":"British Columbia Centre for Excellence in HIV\/AIDS, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Heckerman","sequence":"additional","affiliation":[{"name":"Microsoft Research, eScience Group, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arne","family":"Schneidewind","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M.","family":"Allen","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.9.6103-6110.1994"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.7.4650-4655.1994"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.2.463"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090365"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5403.857"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.6.991"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5265.1167"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.21.2349"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00182-09"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1195271"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(01)02131-1"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5408.1748"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.54.101601.152346"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10003"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1935"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007252"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1890"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/518515"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903227"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-205"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8927-8930.2004"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/415335a"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408773102"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.13.7069-7078.2004"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031982"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.3.375"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041455"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm992"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2405"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830270929"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20022138"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.7.3617-3623.2006"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02356-07"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01543-07"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01970-08"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01882-08"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00465-07"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06682-11"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00708-07"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1520"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.2.882-890.2003"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.6.3122-3125.2006"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06728-11"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01231-06"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.063"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09640"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006687"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01061-08"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi060927x"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00442-4"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1069660"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.2006.0131"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1131528"},{"key":"e_1_3_2_56_2","first-page":"3","volume-title":"HIV molecular immunology 2009, LA-UR 09-05941","author":"Llano A","year":"2009","unstructured":"LlanoA FrahmN BranderC . 2009. How to optimally define optimal cytotoxic T lymphocyte epitopes in HIV infection?, p I-3\u20135. In YusimK KorberB BranderC HaynesB KoupR MooreJP WalkerB WatkinsD (ed), HIV molecular immunology 2009, LA-UR 09-05941. Los Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, NM."},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01998-12"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.8.5000-5005.2005"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01381-12"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-200105010-00002"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200102153440702"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200102000-00005"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199612005-00002"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01369-07"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.21.13239-13249.2005"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.7.3099"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.3979"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M507375200"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000033"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00580-08"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072457"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07746"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e32834981b3"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01086-10"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030403"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.03233-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.03233-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T15:34:11Z","timestamp":1646494451000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.03233-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4]]},"references-count":74,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1128\/JVI.03233-12"],"URL":"https:\/\/doi.org\/10.1128\/jvi.03233-12","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4]]},"assertion":[{"value":"2012-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-01-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}