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

Autoria(s): International HIV Controllers Study; Pereyra F.; Pereyra F.; Jia X.; McLaren P.J.; Telenti A.; de Bakker P.I.; Walker B.D.; Ripke S.; Brumme C.J.; Pulit S.L.; Carrington M.; Kadie C.M.; Carlson J.M.; Heckerman D.; Graham R.R.; Plenge R.M.; Deeks S.G.; Gianniny L.; Crawford G.; Sullivan J.; Gonzalez E.; Davies L.; Camargo A.; Moore J.M.; Beattie N.; Gupta S.; Crenshaw A.; Burtt N.P.; Guiducci C.; Gupta N.; Gao X.; Qi Y.; Yuki Y.; Piechocka-Trocha A.; Cutrell E.; Rosenberg R.; Moss K.L.; Lemay P.; O'Leary J.; Schaefer T.; Verma P.; Toth I.; Block B.; Baker B.; Rothchild A.; Lian J.; Proudfoot J.; Alvino D.M.; Vine S.; Addo M.M.; Allen T.M.; Altfeld M.; Henn M.R.; Le Gall S.; Streeck H.; Haas D.W.; Kuritzkes D.R.; Robbins G.K.; Shafer R.W.; Gulick R.M.; Shikuma C.M.; Haubrich R.; Riddler S.; Sax P.E.; Daar E.S.; Ribaudo H.J.; Agan B.; Agarwal S.; Ahern R.L.; Allen B.L.; Altidor S.; Altschuler E.L.; 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 N.C.; Benson A.M.; Berger J.; Bernard N.F.; Bernard A.M.; Birch C.; Bodner S.J.; Bolan R.K.; Boudreaux E.T.; Bradley M.; Braun J.F.; Brndjar J.E.; Brown S.J.; Brown K.; Brown S.T.; Burack J.; Bush L.M.; Cafaro V.; Campbell O.; Campbell J.; Carlson R.H.; Carmichael J.K.; Casey K.K.; Cavacuiti C.; Celestin G.; Chambers S.T.; Chez N.; Chirch L.M.; Cimoch P.J.; Cohen D.; Cohn L.E.; Conway B.; Cooper D.A.; Cornelson B.; Cox D.T.; Cristofano M.V.; Cuchural G.; Czartoski J.L.; Dahman J.M.; Daly J.S.; Davis B.T.; Davis K.; Davod S.M.; DeJesus E.; Dietz C.A.; Dunham E.; Dunn M.E.; Ellerin T.B.; Eron J.J.; Fangman J.J.; Farel C.E.; Ferlazzo H.; Fidler S.; Fleenor-Ford A.; Frankel R.; Freedberg K.A.; French N.K.; Fuchs J.D.; Fuller J.D.; Gaberman J.; Gallant J.E.; Gandhi R.T.; Garcia E.; Garmon D.; Gathe J.C.; Gaultier C.R.; Gebre W.; Gilman F.D.; Gilson I.; Goepfert P.A.; Gottlieb M.S.; Goulston C.; Groger R.K.; Gurley T.D.; Haber S.; Hardwicke R.; Hardy W.D.; Harrigan P.R.; Hawkins T.N.; Heath S.; Hecht F.M.; Henry W.K.; Hladek M.; Hoffman R.P.; Horton J.M.; Hsu R.K.; Huhn G.D.; Hunt P.; Hupert M.J.; Illeman M.L.; Jaeger H.; Jellinger R.M.; John M.; Johnson J.A.; Johnson K.L.; Johnson H.; Johnson K.; Joly J.; Jordan W.C.; Kauffman C.A.; Khanlou H.; Killian R.K.; Kim A.Y.; Kim D.D.; Kinder C.A.; Kirchner J.T.; Kogelman L.; Kojic E.M.; Korthuis P.T.; Kurisu W.; Kwon D.S.; LaMar M.; Lampiris H.; Lanzafame M.; Lederman M.M.; Lee D.M.; Lee J.M.; Lee M.J.; Lee E.T.; Lemoine J.; Levy J.A.; Llibre J.M.; Liguori M.A.; Little S.J.; Liu A.Y.; Lopez A.J.; Loutfy M.R.; Loy D.; Mohammed D.Y.; Man A.; Mansour M.K.; Marconi V.C.; Markowitz M.; Marques R.; Martin J.N.; Martin H.L.; Mayer K.H.; McElrath M.J.; McGhee T.A.; McGovern B.H.; McGowan K.; McIntyre D.; Mcleod G.X.; Menezes P.; Mesa G.; Metroka C.E.; Meyer-Olson D.; Miller A.O.; Montgomery K.; Mounzer K.C.; Nagami E.H.; Nagin I.; Nahass R.G.; Nelson M.O.; Nielsen C.; Norene D.L.; O'Connor D.H.; Ojikutu B.O.; Okulicz J.; Oladehin O.O.; Oldfield E.C.; Olender S.A.; Ostrowski M.; Owen W.F.; Pae E.; Parsonnet J.; Pavlatos A.M.; Perlmutter A.M.; Pierce M.N.; Pincus J.M.; Pisani L.; Price L.J.; Proia L.; Prokesch R.C.; Pujet H.C.; Ramgopal M.; Rathod A.; Rausch M.; Ravishankar J.; Rhame F.S.; Richards C.S.; Richman D.D.; Rodes B.; Rodriguez M.; Rose R.C.; Rosenberg E.S.; Rosenthal D.; Ross P.E.; Rubin D.S.; Rumbaugh E.; Saenz L.; Salvaggio M.R.; Sanchez W.C.; Sanjana V.M.; Santiago S.; Schmidt W.; Schuitemaker H.; Sestak P.M.; Shalit P.; Shay W.; Shirvani V.N.; Silebi V.I.; Sizemore J.M.; Skolnik P.R.; Sokol-Anderson M.; Sosman J.M.; Stabile P.; Stapleton J.T.; Starrett S.; Stein F.; Stellbrink H.J.; Sterman F.L.; Stone V.E.; Stone D.R.; Tambussi G.; Taplitz R.A.; Tedaldi E.M.; Telenti A.; Theisen W.; Torres R.; Tosiello L.; Tremblay C.; Tribble M.A.; Trinh P.D.; Tsao A.; Ueda P.; Vaccaro A.; Valadas E.; Vanig T.J.; Vecino I.; Vega V.M.; Veikley W.; Wade B.H.; Walworth C.; Wanidworanun C.; Ward D.J.; Warner D.A.; Weber R.D.; Webster D.; Weis S.; Wheeler D.A.; White D.J.; Wilkins E.; Winston A.; Wlodaver C.G.; van't Wout A.; Wright D.P.; Yang O.O.; Yurdin D.L.; Zabukovic B.W.; Zachary K.C.; Zeeman B.; Zhao M.
Data(s)

2010
Resumo

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.
Identificador

http://serval.unil.ch/?id=serval:BIB_7DB03A4B1733

isbn:1095-9203 (Electronic)

pmid:21051598

doi:10.1126/science.1195271

isiid:000285153500069
Idioma(s)

en
Fonte

Science (new York, N.y.), vol. 330, no. 6010, pp. 1551-1557
Palavras-Chave #African Americans/genetics; Alleles; Amino Acids/physiology; Antigen Presentation; CD8-Positive T-Lymphocytes/immunology; Cohort Studies; Disease Progression; European Continental Ancestry Group/genetics; Genes, MHC Class I; Genome-Wide Association Study; HIV Antigens/immunology; HIV Infections/ethnology; HIV Infections/genetics; HIV Long-Term Survivors; HIV-1/immunology; HLA-A Antigens/chemistry; HLA-A Antigens/genetics; HLA-B Antigens/chemistry; HLA-B Antigens/genetics; HLA-C Antigens/chemistry; HLA-C Antigens/genetics; Haplotypes; Hispanic Americans/genetics; Humans; Immunity, Innate; Logistic Models; Models, Molecular; Polymorphism, Single Nucleotide; Protein Conformation; Viral Load
Tipo

info:eu-repo/semantics/article

article
Acesso ao item digital