Selective miRNA Modulation Fails to Activate HIV Replication in In Vitro Latency Models

María Rosa López-Huertas, Matías Morín, Nadia Madrid-Elena, Carolina Gutiérrez, Laura Jiménez-Tormo, Javier Santoyo, Francisco Sanz-Rodríguez, Miguel Ángel Moreno Pelayo, Laura García Bermejo, Santiago Moreno

Research output: Contribution to journalArticlepeer-review

Abstract

HIV remains incurable because of viral persistence in latent reservoirs that are inaccessible to antiretroviral therapy. A potential curative strategy is to reactivate viral gene expression in latently infected cells. However, no drug so far has proven to be successful in vivo in reducing the reservoir, and therefore new anti-latency compounds are needed. We explored the role of microRNAs (miRNAs) in latency maintenance and their modulation as a potential anti-latency strategy. Latency models based on treating resting CD4 T cells with chemokine (C-C motif) ligand 19 (CCL19) or interleukin-7 (IL7) before HIV infection and next-generation sequencing were used to identify the miRNAs involved in HIV latency. We detected four upregulated miRNAs (miRNA-98, miRNA-4516, miRNA-4488, and miRNA-7974). Individual or combined inhibition of these miRNAs was performed by transfection into cells latently infected with HIV. Viral replication, assessed 72 h after transfection, did not increase after miRNA modulation, despite miRNA inhibition and lack of toxicity. Furthermore, the combined modulation of five miRNAs previously associated with HIV latency was not effective in these models. Our results do not support the modulation of miRNAs as a useful strategy for the reversal of HIV latency. As shown with other drugs, the potential of miRNA modulation as an HIV reactivation strategy could be dependent on the latency model used.

Original languageEnglish
Pages (from-to)323-336
Number of pages14
JournalMolecular Therapy - Nucleic Acids
Volume17
Early online date20 Jun 2019
DOIs
Publication statusE-pub ahead of print - 20 Jun 2019

Keywords

  • HIV latency
  • latency-reversing agent
  • LRA
  • HIV latency model
  • CCL19; IL-7
  • miRNA modulation

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