Long noncoding RNA MIR4435-2HG enhances metabolic function of myeloid dendritic cells from HIV-1 elite controllers.

Journal Article (Journal Article)

Restriction of HIV-1 replication in elite controllers (ECs) is frequently attributed to T cell-mediated immune responses, while the specific contribution of innate immune cells is less clear. Here, we demonstrate an upregulation of the host long noncoding RNA (lncRNA) MIR4435-2HG in primary myeloid dendritic cells (mDCs) from ECs. Elevated expression of this lncRNA in mDCs was associated with a distinct immunometabolic profile, characterized by increased oxidative phosphorylation and glycolysis activities in response to TLR3 stimulation. Using functional assays, we show that MIR4435-2HG directly influenced the metabolic state of mDCs, likely through epigenetic mechanisms involving H3K27ac enrichment at an intronic enhancer in the RPTOR gene locus, the main component of the mammalian target of rapamycin complex 1 (mTORC1). Together, these results suggest a role of MIR4435-2HG for enhancing immunometabolic activities of mDCs in ECs through targeted epigenetic modifications of a member of the mTOR signaling pathway.

Full Text

Duke Authors

Cited Authors

  • Hartana, CA; Rassadkina, Y; Gao, C; Martin-Gayo, E; Walker, BD; Lichterfeld, M; Yu, XG

Published Date

  • May 1, 2021

Published In

Volume / Issue

  • 131 / 9

Start / End Page

  • 146136 -

PubMed ID

  • 33938445

Pubmed Central ID

  • PMC8087208

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci146136

Language

  • eng