MALAT1 is important for facilitating HIV-1 latency reversal in latently infected monocytes

Abstract

Long non-coding RNAs (lncRNAs) are long RNA transcripts with length >200 nucleotides that do not encode proteins. They play a crucial role in regulating HIV-1 infection, yet their involvement in myeloid cells remains underexplored. Myeloid cells are susceptible to HIV infection and contribute substantially to the latent HIV reservoir. Therefore, disruption of latency within these reservoirs is crucial for achieving a definite cure. In this study, we aimed to ascertain the role of MALAT1 lncRNA in reversal of HIV-1 latency. Latently HIV-infected cell line, U1 was treated with SAHA, followed by qRT-PCR assays to confirm HIV-1 reactivation, and MALAT1 expression was assessed. The in vitro experiments revealed a significant increase in MALAT1 expression following latency reactivation and HIV-1 infection, while its knockdown using siRNA resulted in suppression of HIV transcription, which implies that MALAT1 play a significant role in facilitating the reversal of HIV-1 latency by promoting HIV transcription. Clinical samples were analysed to measure MALAT1 and pro-inflammatory cytokines expression. The elevated MALAT1 expression in treatment-naïve subjects compared to those on ART and HIV-negative controls suggests its association with HIV replication. Moreover, correlation analysis revealed a positive association between MALAT1 expression and pro-inflammatory cytokines, TNF-α and IP-10. To conclude, MALAT1 lncRNA emerged as a crucial facilitator of HIV-1 latency reversal in latently infected monocytes by inducing the expression of pro-inflammatory factors. These findings highlight that MALAT1 could potentially be explored as the therapeutic intervention to reactivate latent cells in monocytes.