麻省理工学院和哈佛大学Mary Carrington研究团队在研究中取得进展。他们的研究认为CCR5转录的CCR5AS lncRNA调节CCR5，并影响HIV感染和疾病进展。 这一研究成果于2019年7月发表在国际顶尖学术期刊《自然—免疫学》上。

课题组研究人员发现rs1015164标志一个激活转录因子结合位点的变化，并控制反义长非编码RNA (lncRNA) CCR5AS的表达。CCR5AS表达的敲低或增强导致CD4⁺T细胞上CCR5表达的相应变化。近些年来爆发的CCR5AS干扰RNA结合蛋白之间的相互作用和CCR5 3翻译区，保护Raly介导的 CCR5信使RNA的降解。通过抑制CCR5AS可以减少CCR5表达，并减少了体外HIV病毒对CD4⁺T细胞的感染。这些数据代表了全基因组疾病关联的功能重要性，其中lncRNA的表达，影响HIV感染和疾病进展。

据了解，多个基因组研究已经发现了人类免疫缺陷病毒 (HIV)感染的结果和编码HIV受体CCR5基因的内部以及周围多态性之间的关联，但其中相关性最强的位点rs1015164A/G的功能仍然是未知的。

附：英文原文

Title: CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome

Author: Smita Kulkarni, Alexandra Lied, Viraj Kulkarni, 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, Hiroyuki Gatanaga, 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

Issue&Volume:Volume 20 Issue 7, July 2019

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.

DOI: 10.1038/s41590-019-0406-1

Source:https://www.nature.com/articles/s41590-019-0406-1