Li Haiyu, Chi Xiangbo, Li Rong, Ouyang Jing, Chen Yaokai
Department of Infectious Disease, Chongqing Public Health Medical Center, Chongqing, China.
Department of Department of Gastroenterology, Chongqing Public Health Medical Center, Chongqing, China.
Mol Ther Nucleic Acids. 2020 Jun 5;20:754-763. doi: 10.1016/j.omtn.2020.04.011. Epub 2020 Apr 29.
The functions and mechanisms of long non-coding RNAs (lncRNAs) in latent HIV-1 infection are not yet fully understood and warrant further research. In this study, we identified the newly inhibitory lncRNA AK130181 (also named LOC105747689), which is highly expressed in CD4 T lymphocytes latently infected with HIV, using bioinformatics. We also found that AK130181 is involved in HIV-1 latency by inhibiting long terminal repeat (LTR)-driven HIV-1 gene transcription in a nuclear factor κB (NF-κB)-dependent manner. Furthermore, silencing AK130181 significantly reactivates viral production from HIV-1 latently infected Jurkat T cells and primary CD4 T cells. Interestingly, we found that inhibition of AK130181 in resting CD4 T cells from HIV-1-infected individuals treated with highly active antiretroviral therapy significantly increased viral reactivation upon T cell activation in vivo. We provide new insights and a better understanding of lncRNAs that play a role in HIV-1 latency, and suggest that silencing AK130181 expression to activate HIV-1 latently infected cells may be a potential therapeutic target for HIV-infected individuals.
长链非编码RNA（lncRNA）在潜伏性HIV-1感染中的功能和机制尚未完全明确，值得进一步研究。在本研究中，我们通过生物信息学方法鉴定了新的抑制性lncRNA AK130181（也称为LOC105747689），其在潜伏感染HIV的CD4 T淋巴细胞中高表达。我们还发现，AK130181通过以核因子κB（NF-κB）依赖的方式抑制长末端重复序列（LTR）驱动的HIV-1基因转录，从而参与HIV-1潜伏。此外，沉默AK130181可显著重新激活HIV-1潜伏感染的Jurkat T细胞和原代CD4 T细胞中的病毒产生。有趣的是，我们发现，在接受高效抗逆转录病毒治疗的HIV-1感染者的静息CD4 T细胞中抑制AK130181，可显著增加体内T细胞激活后的病毒重新激活。我们为在HIV-1潜伏中起作用的lncRNA提供了新的见解和更好的理解，并表明沉默AK130181表达以激活HIV-1潜伏感染细胞可能是HIV感染者的潜在治疗靶点。
