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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome
Nature Immunology, Volume 20, No. 7, Year 2019
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Description
Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted in a corresponding change in CCR5 expression on CD4+ T cells. CCR5AS interfered with interactions between the RNA-binding protein Raly and the CCR5 3′ untranslated region, protecting CCR5 messenger RNA from Raly-mediated degradation. Reduction in CCR5 expression through inhibition of CCR5AS diminished infection of CD4+ T cells with CCR5-tropic HIV in vitro. These data represent a rare determination of the functional importance of a genome-wide disease association where expression of a lncRNA affects HIV infection and disease progression. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Authors & Co-Authors
Kulkarni, Smita
United States, San Antonio
Texas Biomedical Research Institute
United States, Cambridge
Harvard University
Lied, Alexandra M.
United States, Cambridge
Harvard University
Kulkarni, Viraj
United States, San Antonio
Texas Biomedical Research Institute
United States, Cambridge
Harvard University
Ručević, Marijana
United States, Cambridge
Harvard University
Martin, Maureen P.
United States, Reston
Leidos Inc.
Walker-Sperling, Victoria E.K.
United States, Bethesda
National Institutes of Health Nih
Anderson, Stephen K.
United States, Reston
Leidos Inc.
Singh, Sukhvinder R.
United States, San Antonio
Texas Biomedical Research Institute
McLaren, Paul J.
Canada, Ottawa
Public Health Agency of Canada
Canada, Winnipeg
University of Manitoba
Viard, Mathias
United States, Reston
Leidos Inc.
Naranbhai, Vivek
United States, Cambridge
Harvard University
Lin, Zhansong
Japan, Kumamoto
Kumamoto University
Gatanaga, Hiroyuki
Japan, Kumamoto
Kumamoto University
Japan, Tokyo
National Center for Global Health and Medicine
Oka, Shinichi
Japan, Kumamoto
Kumamoto University
Japan, Tokyo
National Center for Global Health and Medicine
Takiguchi, Masafumi
Japan, Kumamoto
Kumamoto University
Thio, Chloe Lynne
United States, Baltimore
Johns Hopkins University
Margolick, Joseph B.
United States, Baltimore
Johns Hopkins University
Kirk, Gregory D.
United States, Baltimore
Johns Hopkins University
Goedert, James Jerome
United States, Rockville
National Cancer Institute Nci
Deeks, Steven G.
United States, San Francisco
San Francisco General Hospital and Trauma Center
Haas, David William
United States, Nashville
Vanderbilt University School of Medicine
Michael, Nelson L.
United States, Silver Spring
Walter Reed Army Institute of Research
Walker, Bruce D.
United States, Cambridge
Harvard University
United States, Chevy Chase
Howard Hughes Medical Institute
United States, Cambridge
Massachusetts Institute of Technology
Le Gall, Sylvie
United States, Cambridge
Harvard University
Chowdhury, Fatema Z.
United States, Cambridge
Harvard University
Yu, Xu G.
United States, Cambridge
Harvard University
Carrington, Mary N.
United States, Cambridge
Harvard University
United States, Reston
Leidos Inc.
Statistics
Citations: 67
Authors: 27
Affiliations: 15
Identifiers
Doi:
10.1038/s41590-019-0406-1
ISSN:
15292908
Research Areas
Genetics And Genomics
Infectious Diseases