HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C.
A variant 35 kb upstream of the HLA-C gene (-35C/T) was previously shown to associate with HLA-C mRNA expression level and steady-state plasma HIV RNA levels. We genotyped this variant in 1,698 patients of European ancestry with HIV. Individuals with known seroconversion dates were used for disease progression analysis and those with longitudinal viral load data were used for viral load analysis. We further tested cell surface expression of HLA-C in normal donors using an HLA-C-specific antibody. We show that the -35C allele is a proxy for high HLA-C cell surface expression, and that individuals with high-expressing HLA-C alleles progress more slowly to AIDS and control viremia significantly better than individuals with low HLA-C expressing alleles. These data strongly implicate high HLA-C expression levels in more effective control of HIV-1, potentially through better antigen presentation to cytotoxic T lymphocytes or recognition and killing of infected cells by natural killer cells.
Thomas
Rasmi
R
Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, USA.
Apps
Richard
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Qi
Ying
Y
Gao
Xiaojiang
X
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Victoria
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O'hUigin
Colm
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O'Connor
Geraldine
G
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Dongliang
D
Fellay
Jacques
J
Martin
Jeffrey N
JN
Margolick
Joseph
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Goedert
James J
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Buchbinder
Susan
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Kirk
Gregory D
GD
Martin
Maureen P
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Telenti
Amalio
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Bruce D
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D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology / Q000821:virology; D000483:Alleles; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015236:HLA-C Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D019562:Viral Load / Q000235:genetics
D015236:HLA-C Antigens; D012333:RNA, Messenger