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Article ; Online: The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Pereyra, Florencia / Jia, Xiaoming / McLaren, Paul J / Telenti, Amalio / de Bakker, Paul I W / Walker, Bruce D / Ripke, Stephan / Brumme, Chanson J / Pulit, Sara L / Carrington, Mary / Kadie, Carl M / Carlson, Jonathan M / Heckerman, David / Graham, Robert R / Plenge, Robert M / Deeks, Steven G / Gianniny, Lauren / Crawford, Gabriel / Sullivan, Jordan /
Gonzalez, Elena / Davies, Leela / Camargo, Amy / Moore, Jamie M / Beattie, Nicole / Gupta, Supriya / Crenshaw, Andrew / Burtt, Noël P / Guiducci, Candace / Gupta, Namrata / Gao, Xiaojiang / Qi, Ying / Yuki, Yuko / Piechocka-Trocha, Alicja / Cutrell, Emily / Rosenberg, Rachel / Moss, Kristin L / Lemay, Paul / O'Leary, Jessica / Schaefer, Todd / Verma, Pranshu / Toth, Ildiko / Block, Brian / Baker, Brett / Rothchild, Alissa / Lian, Jeffrey / Proudfoot, Jacqueline / Alvino, Donna Marie L / Vine, Seanna / Addo, Marylyn M / Allen, Todd M / Altfeld, Marcus / Henn, Matthew R / Le Gall, Sylvie / Streeck, Hendrik / Haas, David W / Kuritzkes, Daniel R / Robbins, Gregory K / Shafer, Robert W / Gulick, Roy M / Shikuma, Cecilia M / Haubrich, Richard / Riddler, Sharon / Sax, Paul E / Daar, Eric S / Ribaudo, Heather J / Agan, Brian / Agarwal, Shanu / Ahern, Richard L / Allen, Brady L / Altidor, Sherly / Altschuler, Eric L / Ambardar, Sujata / Anastos, Kathryn / Anderson, Ben / Anderson, Val / Andrady, Ushan / Antoniskis, Diana / Bangsberg, David / Barbaro, Daniel / Barrie, William / Bartczak, J / Barton, Simon / Basden, Patricia / Basgoz, Nesli / Bazner, Suzane / Bellos, Nicholaos C / Benson, Anne M / Berger, Judith / Bernard, Nicole F / Bernard, Annette M / Birch, Christopher / Bodner, Stanley J / Bolan, Robert K / Boudreaux, Emilie T / Bradley, Meg / Braun, James F / Brndjar, Jon E / Brown, Stephen J / Brown, Katherine / Brown, Sheldon T / Burack, Jedidiah / Bush, Larry M / Cafaro, Virginia / Campbell, Omobolaji / Campbell, John / Carlson, Robert H / Carmichael, J Kevin / Casey, Kathleen K / Cavacuiti, Chris / Celestin, Gregory / Chambers, Steven T / Chez, Nancy / Chirch, Lisa M / Cimoch, Paul J / Cohen, Daniel / Cohn, Lillian E / Conway, Brian / Cooper, David A / Cornelson, Brian / Cox, David T / Cristofano, Michael V / Cuchural, George / Czartoski, Julie L / Dahman, Joseph M / Daly, Jennifer S / Davis, Benjamin T / Davis, Kristine / Davod, Sheila M / DeJesus, Edwin / Dietz, Craig A / Dunham, Eleanor / Dunn, Michael E / Ellerin, Todd B / Eron, Joseph J / Fangman, John J W / Farel, Claire E / Ferlazzo, Helen / Fidler, Sarah / Fleenor-Ford, Anita / Frankel, Renee / Freedberg, Kenneth A / French, Neel K / Fuchs, Jonathan D / Fuller, Jon D / Gaberman, Jonna / Gallant, Joel E / Gandhi, Rajesh T / Garcia, Efrain / Garmon, Donald / Gathe, Joseph C / Gaultier, Cyril R / Gebre, Wondwoosen / Gilman, Frank D / Gilson, Ian / Goepfert, Paul A / Gottlieb, Michael S / Goulston, Claudia / Groger, Richard K / Gurley, T Douglas / Haber, Stuart / Hardwicke, Robin / Hardy, W David / Harrigan, P Richard / Hawkins, Trevor N / Heath, Sonya / Hecht, Frederick M / Henry, W Keith / Hladek, Melissa / Hoffman, Robert P / Horton, James M / Hsu, Ricky K / Huhn, Gregory D / Hunt, Peter / Hupert, Mark J / Illeman, Mark L / Jaeger, Hans / Jellinger, Robert M / John, Mina / Johnson, Jennifer A / Johnson, Kristin L / Johnson, Heather / Johnson, Kay / Joly, Jennifer / Jordan, Wilbert C / Kauffman, Carol A / Khanlou, Homayoon / Killian, Robert K / Kim, Arthur Y / Kim, David D / Kinder, Clifford A / Kirchner, Jeffrey T / Kogelman, Laura / Kojic, Erna Milunka / Korthuis, P Todd / Kurisu, Wayne / Kwon, Douglas S / LaMar, Melissa / Lampiris, Harry / Lanzafame, Massimiliano / Lederman, Michael M / Lee, David M / Lee, Jean M L / Lee, Marah J / Lee, Edward T Y / Lemoine, Janice / Levy, Jay A / Llibre, Josep M / Liguori, Michael A / Little, Susan J / Liu, Anne Y / Lopez, Alvaro J / Loutfy, Mono R / Loy, Dawn / Mohammed, Debbie Y / Man, Alan / Mansour, Michael K / Marconi, Vincent C / Markowitz, Martin / Marques, Rui / Martin, Jeffrey N / Martin, Harold L / Mayer, Kenneth Hugh / McElrath, M Juliana / McGhee, Theresa A / McGovern, Barbara H / McGowan, Katherine / McIntyre, Dawn / Mcleod, Gavin X / Menezes, Prema / Mesa, Greg / Metroka, Craig E / Meyer-Olson, Dirk / Miller, Andy O / Montgomery, Kate / Mounzer, Karam C / Nagami, Ellen H / Nagin, Iris / Nahass, Ronald G / Nelson, Margret O / Nielsen, Craig / Norene, David L / O'Connor, David H / Ojikutu, Bisola O / Okulicz, Jason / Oladehin, Olakunle O / Oldfield, Edward C / Olender, Susan A / Ostrowski, Mario / Owen, William F / Pae, Eunice / Parsonnet, Jeffrey / Pavlatos, Andrew M / Perlmutter, Aaron M / Pierce, Michael N / Pincus, Jonathan M / Pisani, Leandro / Price, Lawrence Jay / Proia, Laurie / Prokesch, Richard C / Pujet, Heather Calderon / Ramgopal, Moti / Rathod, Almas / Rausch, Michael / Ravishankar, J / Rhame, Frank S / Richards, Constance Shamuyarira / Richman, Douglas D / Rodes, Berta / Rodriguez, Milagros / Rose, Richard C / Rosenberg, Eric S / Rosenthal, Daniel / Ross, Polly E / Rubin, David S / Rumbaugh, Elease / Saenz, Luis / Salvaggio, Michelle R / Sanchez, William C / Sanjana, Veeraf M / Santiago, Steven / Schmidt, Wolfgang / Schuitemaker, Hanneke / Sestak, Philip M / Shalit, Peter / Shay, William / Shirvani, Vivian N / Silebi, Vanessa I / Sizemore, James M / Skolnik, Paul R / Sokol-Anderson, Marcia / Sosman, James M / Stabile, Paul / Stapleton, Jack T / Starrett, Sheree / Stein, Francine / Stellbrink, Hans-Jurgen / Sterman, F Lisa / Stone, Valerie E / Stone, David R / Tambussi, Giuseppe / Taplitz, Randy A / Tedaldi, Ellen M / Theisen, William / Torres, Richard / Tosiello, Lorraine / Tremblay, Cecile / Tribble, Marc A / Trinh, Phuong D / Tsao, Alice / Ueda, Peggy / Vaccaro, Anthony / Valadas, Emilia / Vanig, Thanes J / Vecino, Isabel / Vega, Vilma M / Veikley, Wenoah / Wade, Barbara H / Walworth, Charles / Wanidworanun, Chingchai / Ward, Douglas J / Warner, Daniel A / Weber, Robert D / Webster, Duncan / Weis, Steve / Wheeler, David A / White, David J / Wilkins, Ed / Winston, Alan / Wlodaver, Clifford G / van't Wout, Angelique / Wright, David P / Yang, Otto O / Yurdin, David L / Zabukovic, Brandon W / Zachary, Kimon C / Zeeman, Beth / Zhao, Meng

Science (New York, N.Y.)

2010  Volume 330, Issue 6010, Page(s) 1551–1557

Abstract: Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a ... ...

Abstract Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.
MeSH term(s) Black or African American/genetics ; Alleles ; Amino Acids/physiology ; Antigen Presentation ; CD8-Positive T-Lymphocytes/immunology ; Cohort Studies ; Disease Progression ; Genes, MHC Class I ; Genome-Wide Association Study ; HIV Antigens/immunology ; HIV Infections/ethnology ; HIV Infections/genetics ; HIV Infections/immunology ; HIV Infections/virology ; HIV Long-Term Survivors ; HIV-1/immunology ; HLA-A Antigens/chemistry ; HLA-A Antigens/genetics ; HLA-A Antigens/immunology ; HLA-A Antigens/metabolism ; HLA-B Antigens/chemistry ; HLA-B Antigens/genetics ; HLA-B Antigens/immunology ; HLA-B Antigens/metabolism ; HLA-C Antigens/chemistry ; HLA-C Antigens/genetics ; HLA-C Antigens/immunology ; HLA-C Antigens/metabolism ; Haplotypes ; Hispanic or Latino/genetics ; Humans ; Immunity, Innate ; Logistic Models ; Models, Molecular ; Polymorphism, Single Nucleotide ; Protein Conformation ; Viral Load ; White People/genetics
Chemical Substances Amino Acids ; HIV Antigens ; HLA-A Antigens ; HLA-B Antigens ; HLA-C Antigens
Language English
Publishing date 2010-11-04
Publishing country United States
Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID 128410-1
ISSN 1095-9203 ; 0036-8075
ISSN (online) 1095-9203
ISSN 0036-8075
DOI 10.1126/science.1195271
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