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CCR5ASlncRNA variation differentially regulates CCR5, influencing HIV disease outcome Smita Kulkarni, Alexandra Lied, VirajKulkarni, Marijana Rucevic, Maureen P. Martin, Victoria Walker-Sperling,Stephen K. Anderson, Rodger Ewy, Sukhvinder Singh, Hoang Nguyen, Paul J.McLaren, Mathias Viard, Vivek Naranbhai, Chengcheng Zou, Zhansong Lin, HiroyukiGatanaga, Shinichi Oka, Masafumi Takiguchi, Chloe L. Thio, Joseph Margolick,Gregory D. Kirk, James J. Goedert, W. Keith Hoots, Steven G. Deeks, David W.Haas, Nelson Michael, Bruce Walker, Sylvie Le Gall, Fatema Z. Chowdhury, Xu G.Yu & Mary Carrington Nat Immunol. pub date:2019-6-17 doi:10.1038/s41590-019-0406-1 Abstract: Multiple genome-wide studies have identified associationsbetween outcome of human immunodeficiency virus (HIV) infection andpolymorphisms in and around the gene encoding the HIV co-receptor CCR5, but thefunctional basis for the strongest of these associations, rs1015164A/G, isunknown. We found that rs1015164 marks variation in an activating transcriptionfactor 1 binding site that controls expression of the antisense long noncodingRNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted ina corresponding change in CCR5 expression on CD4+ T cells. CCR5AS interferedwith interactions between the RNA-binding protein Raly and the CCR5 3' untranslatedregion, protecting CCR5 messenger RNA from Raly-mediated degradation. Reductionin CCR5 expression through inhibition of CCR5AS diminished infection of CD4+ Tcells with CCR5-tropic HIV in vitro. These data represent a rare determinationof the functional importance of a genome-wide disease association whereexpression of a lncRNA affects HIV infection and disease progression. 推荐理由： 这篇文章代表了全基因组疾病关联的功能重要性的罕见确定，其中lncRNA的表达影响HIV感染和疾病进展。
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