@article{b186c29db3924a0da8f9106829160f14,
title = "CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome",
abstract = "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.",
author = "Smita Kulkarni and Alexandra Lied and Viraj Kulkarni and Marijana Rucevic and Martin, {Maureen P.} and Victoria Walker-Sperling and Anderson, {Stephen K.} and Rodger Ewy and Sukhvinder Singh and Hoang Nguyen and McLaren, {Paul J.} and Mathias Viard and Vivek Naranbhai and Chengcheng Zou and Zhansong Lin and Hiroyuki Gatanaga and Shinichi Oka and Masafumi Takiguchi and Thio, {Chloe L.} and Joseph Margolick and Kirk, {Gregory D.} and Goedert, {James J.} and Hoots, {W. Keith} and Deeks, {Steven G.} and Haas, {David W.} and Nelson Michael and Bruce Walker and {Le Gall}, Sylvie and Chowdhury, {Fatema Z.} and Yu, {Xu G.} and Mary Carrington",
note = "Funding Information: The project was supported by NIAID (grant nos AI120900 and AI140956 to S.K.), HU-CFAR (to S.K.), Cowles fellowship (to S.S.), institutional funds from the Texas Biomedical Research Institute and the Ragon Institute of MGH, MIT and Harvard. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory (contract no. HHSN261200800001E). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab and Center for Cancer Research. See extended acknowledgements in Supplementary Information for full details. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = jul,
day = "1",
doi = "10.1038/s41590-019-0406-1",
language = "English (US)",
volume = "20",
pages = "824--834",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "7",
}