Long Non-coding RNA NKILA Regulates HIV-1 Replication And Latency Through Repressing NF-?B Signaling

Human immunodeficiency virus(Human Immunodeficiency Virus,HIV)is the main pathogen of acquired immunodeficiency syndrome-AIDS.At present,about 37.9 million people worldwide are infected with HIV,which is still a major infectious disease that seriously threatens human health.Through the continuous efforts of scientists,antiviral therapy has been able to control the disease and make it a chronic disease,but has not yet developed A complete cure for AIDS.In recent years,scientists have discovered that some long-chain non-coding RNAs(LncRNA)that exist in the human body have a wide range of biological effects,including important regulatory effects on cancer,viral infections and other diseases,although some long-chain non-coding RNAs have been reported HIV-1 plays an important role in the replication process,but there is still little research on the regulation of HIV by long non-coding RNA.With the deepening of research,LncRNA NKILA has recently been identified as a negative regulator of NF-?B signaling and plays an important role in the development of various cancers;it is well known that in the life cycle of HIV-1,its transcription and latency Reactivation requires NF-?B-mediated activation of HIV-1 LTR-driven gene expression.Therefore,does LncRNA NKILA play an important role in HIV-1 replication and latency,and is its role achieved by regulating the NF-?B signaling pathway? Therefore,in response to this important scientific issue,we carried out research on the effect of NKILA on HIV-1 replication and its mechanism of action.In this study,we first demonstrated that lncRNA NKILA plays a key role in regulating HIV-1 transcription and replication.We found that NKILA strongly inhibited HIV-1 replication and its infectivity in a dose-dependent manner;further studies found that NKILA inhibited HIV-1 LTR activity in a gradient-dependent manner;we knew that HIV-1 LTR contained NF-?b binding This study confirmed that NKILA binds to the NF-?B subunit P65 through its hairpin structure,thereby binding to the P65: P50: l?B? complex and further masking the phosphorylation site of l?B?,thereby inhibiting NF-?B signaling,And ultimately inhibit LTR activity.And in this process,NKILA not only inhibits LTR activity,but also inhibits LTR activity induced by Tat alone and LTR activity induced by both P65 and Tat.Next,in order to prove whether NKILA can be used as a new broad-spectrum antiviral molecule against HIV replication,we conducted a more in-depth study.The study found that NKILA can also inhibit the replication of HIV-1 subtypes of different cell tropisms,such as AD8 strain of macrophage tropism,YU2 strain from the brain and R5X4-tropic 89.6 strain.Therefore,we believe that LncRNA NKILA is an HIV inhibitor with a broad-spectrum antiviral effect.In addition,this study also found that HIV-1 replication or reactivation significantly downregulated T cells including Jurkat,H9,isolated primary CD4 + cells and HIV-1 latent cells,and NKILA in PBMC of patients infected with HIV-1.Expression,these results indicate that HIV-1 downregulates the expression of NKILA in order to overcome the inhibitory effect of NIKLA,thereby achieving HIV-1 replication.These findings strengthen our understanding of the functional inhibition of HIV-1 replication and latency by lncRNA NKILA through NF-?B signaling,and provide promising therapeutic strategies for HIV-1.