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Erschienen in: Medical Microbiology and Immunology 2/2012

01.05.2012 | Original Investigation

Control of M184V HIV-1 mutants by CD8 T-cell responses

verfasst von: Thomas Vollbrecht, Josef Eberle, Julia Roider, Silja Bühler, Renate Stirner, Nadja Henrich, Ulrich Seybold, Johannes R. Bogner, Rika Draenert

Erschienen in: Medical Microbiology and Immunology | Ausgabe 2/2012

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Abstract

Antiretroviral treatment directed against HIV is highly effective, yet limited by drug resistance mutations. We hypothesized that CD8 T cells targeting drug-resistant HIV mutants are able to inhibit viral replication in the setting of a failing therapeutic regimen. We evaluated CD8 T-cell responses and mapped epitopes in HIV-infected patients by interferon-gamma Elispot and intracellular cytokine staining. Autologous virus was sequenced by RT-PCR. Viral replication inhibition assays were performed using M184V mutant virus and CD8 T cell lines. CD8 T-cell responses toward the regions of viral drug resistance mutations in Pol are frequent. Focusing on the M184V mutation, A*02:01-YQYVDDLYV and A*02:01-VIYQYVDDLYV were identified as optimal epitopes for the majority of study subjects. Viral replication of M184V HIV mutants was inhibited by CD8 T cell lines in vitro. In case of a failing lamivudine/emtricitabine containing regimen, individuals with a CD8 T-cell response toward M184V had a significant lower viral load than those without a CD8 response (p = 0.005). Two study subjects even achieved an undetectable viral load. Our data suggest that control of M184V mutant virus by CD8 T-cell responses is possible in vitro and in vivo. This control has important implications for therapeutic vaccination strategies.
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Science 330(6010):1551–1557. doi:10.1126/science.1195271 Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, Ripke S, Brumme CJ, Pulit SL, Carrington M, Kadie CM, Carlson JM, Heckerman D, Graham RR, Plenge RM, Deeks SG, Gianniny L, Crawford G, Sullivan J, Gonzalez E, Davies L, Camargo A, Moore JM, Beattie N, Gupta S, Crenshaw A, Burtt NP, Guiducci C, Gupta N, Gao X, Qi Y, Yuki Y, Piechocka-Trocha A, Cutrell E, Rosenberg R, Moss KL, Lemay P, O’Leary J, Schaefer T, Verma P, Toth I, Block B, Baker B, Rothchild A, Lian J, Proudfoot J, Alvino DM, Vine S, Addo MM, Allen TM, Altfeld M, Henn MR, Le Gall S, Streeck H, Haas DW, Kuritzkes DR, Robbins GK, Shafer RW, Gulick RM, Shikuma CM, Haubrich R, Riddler S, Sax PE, Daar ES, Ribaudo HJ, Agan B, Agarwal S, Ahern RL, Allen BL, Altidor S, Altschuler EL, Ambardar S, Anastos K, Anderson B, Anderson V, Andrady U, Antoniskis D, Bangsberg D, Barbaro D, Barrie W, Bartczak J, Barton S, Basden P, Basgoz N, Bazner S, Bellos NC, Benson AM, Berger J, Bernard NF, Bernard AM, Birch C, Bodner SJ, Bolan RK, Boudreaux ET, Bradley M, Braun JF, Brndjar JE, Brown SJ, Brown K, Brown ST, Burack J, Bush LM, Cafaro V, Campbell O, Campbell J, Carlson RH, Carmichael JK, Casey KK, Cavacuiti C, Celestin G, Chambers ST, Chez N, Chirch LM, Cimoch PJ, Cohen D, Cohn LE, Conway B, Cooper DA, Cornelson B, Cox DT, Cristofano MV, Cuchural G Jr, Czartoski JL, Dahman JM, Daly JS, Davis BT, Davis K, Davod SM, DeJesus E, Dietz CA, Dunham E, Dunn ME, Ellerin TB, Eron JJ, Fangman JJ, Farel CE, Ferlazzo H, Fidler S, Fleenor-Ford A, Frankel R, Freedberg KA, French NK, Fuchs JD, Fuller JD, Gaberman J, Gallant JE, Gandhi RT, Garcia E, Garmon D, Gathe JC Jr, Gaultier CR, Gebre W, Gilman FD, Gilson I, Goepfert PA, Gottlieb MS, Goulston C, Groger RK, Gurley TD, Haber S, Hardwicke R, Hardy WD, Harrigan PR, Hawkins TN, Heath S, Hecht FM, Henry WK, Hladek M, Hoffman RP, Horton JM, Hsu RK, Huhn GD, Hunt P, Hupert MJ, Illeman ML, Jaeger H, Jellinger RM, John M, Johnson JA, Johnson KL, Johnson H, Johnson K, Joly J, Jordan WC, Kauffman CA, Khanlou H, Killian RK, Kim AY, Kim DD, Kinder CA, Kirchner JT, Kogelman L, Kojic EM, Korthuis PT, Kurisu W, Kwon DS, LaMar M, Lampiris H, Lanzafame M, Lederman MM, Lee DM, Lee JM, Lee MJ, Lee ET, Lemoine J, Levy JA, Llibre JM, Liguori MA, Little SJ, Liu AY, Lopez AJ, Loutfy MR, Loy D, Mohammed DY, Man A, Mansour MK, Marconi VC, Markowitz M, Marques R, Martin JN, Martin HL Jr, Mayer KH, McElrath MJ, McGhee TA, McGovern BH, McGowan K, McIntyre D, McLeod GX, Menezes P, Mesa G, Metroka CE, Meyer-Olson D, Miller AO, Montgomery K, Mounzer KC, Nagami EH, Nagin I, Nahass RG, Nelson MO, Nielsen C, Norene DL, O’Connor DH, Ojikutu BO, Okulicz J, Oladehin OO, Oldfield EC IIIrd, Olender SA, Ostrowski M, Owen WF Jr, Pae E, Parsonnet J, Pavlatos AM, Perlmutter AM, Pierce MN, Pincus JM, Pisani L, Price LJ, Proia L, Prokesch RC, Pujet HC, Ramgopal M, Rathod A, Rausch M, Ravishankar J, Rhame FS, Richards CS, Richman DD, Rodes B, Rodriguez M, Rose RC, 3rd, Rosenberg ES, Rosenthal D, Ross PE, Rubin DS, Rumbaugh E, Saenz L, Salvaggio MR, Sanchez WC, Sanjana VM, Santiago S, Schmidt W, Schuitemaker H, Sestak PM, Shalit P, Shay W, Shirvani VN, Silebi VI, Sizemore JM Jr, Skolnik PR, Sokol-Anderson M, Sosman JM, Stabile P, Stapleton JT, Starrett S, Stein F, Stellbrink HJ, Sterman FL, Stone VE, Stone DR, Tambussi G, Taplitz RA, Tedaldi EM, Theisen W, Torres R, Tosiello L, Tremblay C, Tribble MA, Trinh PD, Tsao A, Ueda P, Vaccaro A, Valadas E, Vanig TJ, Vecino I, Vega VM, Veikley W, Wade BH, Walworth C, Wanidworanun C, Ward DJ, Warner DA, Weber RD, Webster D, Weis S, Wheeler DA, White DJ, Wilkins E, Winston A, Wlodaver CG, van’t Wout A, Wright DP, Yang OO, Yurdin DL, Zabukovic BW, Zachary KC, Zeeman B, Zhao M The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330(6010):1551–1557. doi:10.​1126/​science.​1195271
Metadaten
Titel
Control of M184V HIV-1 mutants by CD8 T-cell responses
verfasst von
Thomas Vollbrecht
Josef Eberle
Julia Roider
Silja Bühler
Renate Stirner
Nadja Henrich
Ulrich Seybold
Johannes R. Bogner
Rika Draenert
Publikationsdatum
01.05.2012
Verlag
Springer-Verlag
Erschienen in
Medical Microbiology and Immunology / Ausgabe 2/2012
Print ISSN: 0300-8584
Elektronische ISSN: 1432-1831
DOI
https://doi.org/10.1007/s00430-011-0222-1

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