Publication
Title: Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells
Authors: Ramsuran V, Vivek Naranbhai, Amir Horowitz, Ying Qi, Maureen P. Martin, Yuko Yuki, Xiaojiang Gao, Victoria Walker-Sperling, Gregory Q. Del Prete, Douglas K. Schneider, Jeffrey D. Lifson, Jacques Fellay, Steven G. Deeks, Jeffrey N. Martin, James J. Goedert, Steven M. Wolinsky, Nelson L. Michael, Gregory D. Kirk, Susan Buchbinder, David Haas, Thumbi Ndung'u, Philip Goulder, Peter Parham, Bruce D. Walker, Jonathan M. Carlson and Mary Carrington.
Journal: Science,359:86-90 (2018)
Abstract
The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease.
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Citation: Ramsuran V, Vivek Naranbhai, Amir Horowitz, Ying Qi, Maureen P. Martin, Yuko Yuki, Xiaojiang Gao, Victoria Walker-Sperling, Gregory Q. Del Prete, Douglas K. Schneider, Jeffrey D. Lifson, Jacques Fellay, Steven G. Deeks, Jeffrey N. Martin, James J. Goedert, Steven M. Wolinsky, Nelson L. Michael, Gregory D. Kirk, Susan Buchbinder, David Haas, Thumbi Ndung'u, Philip Goulder, Peter Parham, Bruce D. Walker, Jonathan M. Carlson and Mary Carrington. Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells Science,359:86-90 (2018).
Media Coverage of this Publication:
Science Discovery: Biomarkers for HIV treatment - KRISP News - 2018-01-19
Mercury Reporter, Durban, KwaZulu-Natal, 19 Jan 2018: Scientists led an in ternational research team which discovered new genetic markers that identify why the onset of Aids appears to occur so quickly in some people after they are infected with HIV The study published in the journal Science (Ramsuran et al. Science 2018), sheds new light on how specific human genes can lead to a faster deterioration for people living with HIV who are not on treatment.
SA study reveals important link between genes and Aids - KRISP News - 2018-01-19
HIV/AIDS researchers have never understood why people infected with HIV developed Aids at different times? but now they suspect that it all has to do with their genes. A study by South African and US researchers (Ramsuran et al. Science 2018) has shed new light on how specific genes in people can lead to the faster progression of Aids-related illnesses in people living with HIV who are not on treatment.
Why some HIV-positive people develop AIDS quicker than others is now clearer - KRISP News - 2018-01-19
The study, published in the prestigious journal Science (Ramsuram et al. 2018), was led by South African scientists who, together with an international research team, discovered that a specific-type human leucocyte antigen (HLA) gene helps infected cells to evade the body's first line of defence
Science Editorial: Inhibiting natural killer cells in AIDS - KRISP Papers - 2018-01-04
The human leukocyte antigen (HLA) gene complex varies enormously among individuals and helps explain individual variation in immunity to infectious diseases. Ramsuran et al. (Science 2018) examined data from almost 10,000 HIV infections.
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