title: HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C.
abstract: 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.
authors: Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland, USA.
authors: Rasmi
authors: R
authors: Thomas
authors: Richard
authors: R
authors: Apps
authors: Ying
authors: Y
authors: Qi
authors: Xiaojiang
authors: X
authors: Gao
authors: Victoria
authors: V
authors: Male
authors: Colm
authors: C
authors: O'hUigin
authors: Geraldine
authors: G
authors: O'Connor
authors: Dongliang
authors: D
authors: Ge
authors: Jacques
authors: J
authors: Fellay
authors: Jeffrey N
authors: JN
authors: Martin
authors: Joseph
authors: J
authors: Margolick
authors: James J
authors: JJ
authors: Goedert
authors: Susan
authors: S
authors: Buchbinder
authors: Gregory D
authors: GD
authors: Kirk
authors: Maureen P
authors: MP
authors: Martin
authors: Amalio
authors: A
authors: Telenti
authors: Steven G
authors: SG
authors: Deeks
authors: Bruce D
authors: BD
authors: Walker
authors: David
authors: D
authors: Goldstein
authors: Daniel W
authors: DW
authors: McVicar
authors: Ashley
authors: A
authors: Moffett
authors: Mary
authors: M
authors: Carrington
mesh_terms: 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
chemical_list: D015236:HLA-C Antigens; D012333:RNA, Messenger