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Copy number variation of KIR genes influences HIV-1 control
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نویسنده
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pelak k. ,need a.c. ,fellay j. ,shianna k.v. ,feng s. ,urban t.j. ,ge d. ,de luca a. ,martinez-picado j. ,wolinsky s.m. ,martinson j.j. ,jamieson b.d. ,bream j.h. ,martin m.p. ,borrow p. ,letvin n.l. ,mcmichael a.j. ,haynes b.f. ,telenti a. ,and university of lausanne lausanne ,carrington m. ,goldstein d.b. ,alter g.
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منبع
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plos biology - 2011 - دوره : 9 - شماره : 11
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چکیده
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A genome-wide screen for large structural variants showed that a copy number variant (cnv) in the region encoding killer cell immunoglobulin-like receptors (kir) associates with hiv-1 control as measured by plasma viral load at set point in individuals of european ancestry. this cnv encompasses the kir3dl1-kir3ds1 locus,encoding receptors that interact with specific hla-bw4 molecules to regulate the activation of lymphocyte subsets including natural killer (nk) cells. we quantified the number of copies of kir3ds1 and kir3dl1 in a large hiv-1 positive cohort,and showed that an increase in kir3ds1 count associates with a lower viral set point if its putative ligand is present (p = 0.00028),as does an increase in kir3dl1 count in the presence of kir3ds1 and appropriate ligands for both receptors (p = 0.0015). we further provide functional data that demonstrate that nk cells from individuals with multiple copies of kir3dl1,in the presence of kir3ds1 and the appropriate ligands,inhibit hiv-1 replication more robustly,and associated with a significant expansion in the frequency of kir3ds1+,but not kir3dl1+,nk cells in their peripheral blood. our results suggest that the relative amounts of these activating and inhibitory kir play a role in regulating the peripheral expansion of highly antiviral kir3ds1+ nk cells,which may determine differences in hiv-1 control following infection. © 2011 pelak et al.
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آدرس
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center for human genome variation,duke university school of medicine,durham,nc, United States, center for human genome variation,duke university school of medicine,durham,nc, United States, center for human genome variation,duke university school of medicine,durham,nc,united states,global health institute,school of life sciences,ecole polytechnique fédérale de lausanne,lausanne, Switzerland, center for human genome variation,duke university school of medicine,durham,nc, United States, department of biostatistics and bioinformatics,duke university,durham,nc, United States, center for human genome variation,duke university school of medicine,durham,nc, United States, center for human genome variation,duke university school of medicine,durham,nc, United States, institute of clinical infectious diseases,catholic university of the sacred heart,rome,italy,division of infectious diseases,siena university hospital,siena, Italy, irsicaixa foundation and hospital germans trias i pujol,badalona,spain,institució catalana de recerca i estudis avançats,barcelona, Spain, division of infectious diseases,northwestern university feinberg school of medicine,chicago,il, United States, infectious diseases and microbiology,graduate school of public health,university of pittsburgh,pittsburgh,pa, United States, department of medicine,david geffen school of medicine,university of california-los angeles,los angeles,ca, United States, department of molecular microbiology and immunology,johns hopkins bloomberg school of public health,baltimore,md, United States, cancer and inflammation program,laboratory of experimental immunology,saic-frederick,inc.,nci-frederick,frederick,md, United States, nuffield department of clinical medicine,university of oxford and weatherall institute of molecular medicine,john radcliffe hospital,headington,oxford, United Kingdom, division of viral pathogenesis,beth israel deaconess medical center,harvard medical school,boston,ma, United States, medical research council human immunology unit,weatherall institute of molecular medicine,john radcliffe hospital,oxford, United Kingdom, duke human vaccine institute,duke university,durham,nc, United States, institute of microbiology, University Hospital Center, department of medicine,david geffen school of medicine,university of california-los angeles,los angeles,ca,united states,ragon institute of mgh,mit and harvard,boston,ma, United States, center for human genome variation,duke university school of medicine,durham,nc, United States, ragon institute of mgh,mit and harvard,boston,ma, United States
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Authors
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k. ,a.c. ,j. ,k.v. ,s. ,t.j. ,d. ,a. ,j. ,s.m. ,j.j. ,b.d. ,j.h. ,m.p. ,p. ,n.l. ,a.j. ,b.f. ,a. ,lausanne ,m. ,d.b. ,g.
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