Short Communication: Long Noncoding RNA GAS5 Inhibits HIV-1 Replication Through Interaction with miR-873

Abstract

HIV is the causative pathogen of AIDS, which has generated worldwide concern. Long noncoding RNAs (lncRNAs) are a rising star in virus-host cross-talk pathways; they are differentially expressed during many viral infections and are involved in multiple biological processes. Currently, lncRNA growth arrest-specific transcript 5 (GAS5) is known to be downregulated during HIV-1 infection. However, the functions and mechanisms of GAS5 in HIV-1 infection remain largely unknown. In this report, it was found for the first time that GAS5 could inhibit HIV-1 replication. Interestingly, using bioinformatics analyses (with Genomica and starBase.v2.0), GAS5 was found to potentially interact with miR-873. It was further verified that GAS5 could suppress miR-873. Moreover, miR-873 could promote HIV-1 replication. Together, these results not only suggest that GAS5 may inhibit HIV-1 replication through interaction with miR-873 but the results may also provide novel biomarkers for antiviral drugs or potential targets for future therapeutics for HIV/AIDS.

Long noncoding RNA GAS5 does not regulate HBV replication

“…This suggested that GAS5 may regulate virus replication specifically. Moreover, GAS5 was decreased in HIV‐1 infection while it was greatly increased along with the progression of HCV infection . Our work indicated GAS5 could be stimulated by HBV in both HepAD38 cell and HepG2 cell.…”

“…Based on the existing evidence and our study, we speculated the functions and expression patterns of GAS5 vary in different virus infections in host cells. Upon HIV infection, dual‐luciferase reporter assays indicated that GAS5 could bind to HIV‐1 NL4‐3 by competing with miR‐873 in exon 7, leading to the reduce of both HIV gag and pol . In addition, by applying the RNA‐protein interaction prediction algorithm and RNA immunoprecipitation assay, Xijing Qian found GAS5 5′ end 200 sequences directly bind to HCV protease NS3 protein which is essential for viral replication .…”

“…GAS5 acted as a suppressor of HCV replication by binding to HCV NS3 protein and modulating innate immunity . In addition, GAS5 inhibited HIV‐1 replication through the interaction with miR‐873 as a competing endogenous RNA (ceRNA) although it was downregulated in HIV‐1 infection . However, the contribution of GAS5 in HBV infection especially HBV replication has not been investigated.…”

Long Non-coding RNAs Mechanisms of Action in HIV-1 Modulation and the Identification of Novel Therapeutic Targets

“…The lncRNA growth arrest-specific transcript 5 (GAS5) inhibits HIV-1 replication by acting as a competing endogenous RNA (ceRNA), suppressing the effects of miR-873 [12]. GAS5 has been shown to be downregulated upon HIV-1 infection in T cells [54] and, using a combination of knockdown and overexpression strategies of GAS5, Chen et al (2018) determined that high levels of GAS5 decreased HIV-1 transcription, while a knockdown of GAS5 resulted in an increase in HIV-1 transcription.…”

“…LncRNAs work in cis or trans, or both, to exert their gene modulatory effects. These modulatory effects can occur in a myriad of ways, including: recruitment of chromatin remodeling factors to either repress or de-repress gene expression [6]; working as enhancers to facilitate promoter-enhancer interactions [7,8]; acting as an inhibitor to RNA polymerase II (RNAPII) binding through transcriptional interference [9]; acting as a scaffold for regulatory proteins at target sites in the DNA [10]; as competitive endogenous RNAs (ceRNAs), acting as microRNA sponges [11,12] or as decoys [13,14]; through facilitating mRNA splicing [15]; as well as manipulating target protein function by directing changes in phosphorylation states [16]; all of which result in a change in gene expression. With such distinct molecular mechanisms attributed to a small percentage of characterized lncRNAs, we are now only beginning to uncover the scope of how these regulatory molecules function in vivo.…”