Copy number variation of KIR genes influences HIV-1 control.
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...
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2011
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oai:doaj.org-article:a88a6a17ab4c48cbaa44f406101588bf2021-11-18T05:36:52ZCopy number variation of KIR genes influences HIV-1 control.1544-91731545-788510.1371/journal.pbio.1001208https://doaj.org/article/a88a6a17ab4c48cbaa44f406101588bf2011-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22140359/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885A 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.Kimberly PelakAnna C NeedJacques FellayKevin V ShiannaSheng FengThomas J UrbanDongliang GeAndrea De LucaJavier Martinez-PicadoSteven M WolinskyJeremy J MartinsonBeth D JamiesonJay H BreamMaureen P MartinPersephone BorrowNorman L LetvinAndrew J McMichaelBarton F HaynesAmalio TelentiMary CarringtonDavid B GoldsteinGalit AlterNIAID Center for HIV/AIDS Vaccine ImmunologyPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 9, Iss 11, p e1001208 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
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EN |
| topic |
Biology (General) QH301-705.5 |
| spellingShingle |
Biology (General) QH301-705.5 Kimberly Pelak Anna C Need Jacques Fellay Kevin V Shianna Sheng Feng Thomas J Urban Dongliang Ge Andrea De Luca Javier Martinez-Picado Steven M Wolinsky Jeremy J Martinson Beth D Jamieson Jay H Bream Maureen P Martin Persephone Borrow Norman L Letvin Andrew J McMichael Barton F Haynes Amalio Telenti Mary Carrington David B Goldstein Galit Alter NIAID Center for HIV/AIDS Vaccine Immunology Copy number variation of KIR genes influences HIV-1 control. |
| description |
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. |
| format |
article |
| author |
Kimberly Pelak Anna C Need Jacques Fellay Kevin V Shianna Sheng Feng Thomas J Urban Dongliang Ge Andrea De Luca Javier Martinez-Picado Steven M Wolinsky Jeremy J Martinson Beth D Jamieson Jay H Bream Maureen P Martin Persephone Borrow Norman L Letvin Andrew J McMichael Barton F Haynes Amalio Telenti Mary Carrington David B Goldstein Galit Alter NIAID Center for HIV/AIDS Vaccine Immunology |
| author_facet |
Kimberly Pelak Anna C Need Jacques Fellay Kevin V Shianna Sheng Feng Thomas J Urban Dongliang Ge Andrea De Luca Javier Martinez-Picado Steven M Wolinsky Jeremy J Martinson Beth D Jamieson Jay H Bream Maureen P Martin Persephone Borrow Norman L Letvin Andrew J McMichael Barton F Haynes Amalio Telenti Mary Carrington David B Goldstein Galit Alter NIAID Center for HIV/AIDS Vaccine Immunology |
| author_sort |
Kimberly Pelak |
| title |
Copy number variation of KIR genes influences HIV-1 control. |
| title_short |
Copy number variation of KIR genes influences HIV-1 control. |
| title_full |
Copy number variation of KIR genes influences HIV-1 control. |
| title_fullStr |
Copy number variation of KIR genes influences HIV-1 control. |
| title_full_unstemmed |
Copy number variation of KIR genes influences HIV-1 control. |
| title_sort |
copy number variation of kir genes influences hiv-1 control. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/a88a6a17ab4c48cbaa44f406101588bf |
| work_keys_str_mv |
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| _version_ |
1718424869783207936 |