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| Content Provider | frontiers |
|---|---|
| Author | Madrid-Elena, Nadia Serrano-Villar, Sergio Gutiérrez, Carolina Sastre, Beatriz Morín, Matías Luna, Laura Martín, Laura Santoyo-López, Javier López-Huertas, María Rosa Moreno, Elena García-Bermejo, María Laura Moreno-Pelayo, Miguel Ángel Moreno, Santiago |
| Abstract | miRNAs dictate relevant virus-host interactions, offering new avenues for interventions to achieve an HIV remission. We aimed to enhance HIV-specific cytotoxic responses—a hallmark of natural HIV control— by miRNA modulation in T cells. We recruited the next 12 individuals; six elite controllers and six were individuals with chronic HIV infection on long-term antiretroviral therapy. Elite controllers exhibited stronger HIV-specific cytotoxic responses than the progressors, and their CD8+T cells showed a miRNA (hsa-miR-10a-5p) significantly downregulated. When we transfected ex vivo CD8+ T cells from progressors with a synthetic miR-10a-5p inhibitor, miR-10a-5p levels decreased in 4 out of 6 progressors, correlating with an increase in HIV-specific cytotoxic responses. The effects of miR-10a-5p inhibition on HIV-specific CTL responses were modest, short-lived, and occurred before day seven after modulation. IL-4 and TNF-α levels strongly correlated with HIV-specific cytotoxic capacity. Thus, inhibition of miR-10a-5p enhanced HIV-specific CD8+ T cell capacity in progressors. Our pilot study proves the concept that miRNA modulation is a feasible strategy to combat HIV persistence by enhancing specific cytotoxic immune responses, which will inform new approaches for achieving an antiretroviral therapy-free HIV remission. |
| ISSN | 16643224 |
| DOI | 10.3389/fimmu.2022.998368 |
| Volume Number | 13 |
| Journal | Frontiers in Immunology |
| Language | English |
| Publisher Date | 2022-09-26 |
| Access Restriction | Open |
| Subject Keyword | Cytotoxicity HIV Micro-RNA Cellular immunity Non-coding RNA |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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