Hsa-miR-31 Governs T-Cell Homeostasis in HIV Protection via IFN-γ-Stat1-T-Bet Axis

Lingyan Zhu, Chao Qiu, Lili Dai, Linxia Zhang, Meiqi Feng, Yu Yang, Chenli Qiu, Anli Zhang, Jun Huang, Ying Wang, Ying Wan, Chen Zhao, Hao Wu, Jianxin Lyu, Xiaoyan Zhang, Jianqing Xu

Abstract

It remains poorly defined whether any human miRNAs play protective roles during HIV infection. Here, focusing on a unique cohort of HIV-infected former blood donors, we identified miR-31 (hsa-miR-31) by comparative miRNA profiling as the only miRNA inversely correlating with disease progression. We further validated this association in two prospective cohort studies. Despite conservation during evolution, hsa-miR-31, unlike its mouse counterpart (mmu-miR-31), was downregulated in human T cell upon activation. Our ex vivo studies showed that inhibiting miR-31 in naïve CD4+ T cells promoted a transcriptional profile with activation signature. Consistent with this skewing effect, miR-31 inhibition led to remarkably increased susceptibility to HIV infection. The suppressive nature of miR-31 in CD4+ T cell activation was pinpointed to its ability to decrease T-bet, the key molecule governing IFN-γ production and activation of CD4+ T cells, by directly targeting the upstream STAT1 transcriptional factor for downregulation, thus blunting Th1 response. Our results implicated miR-31 as a useful biomarker for tracking HIV disease progression and, by demonstrating its importance in tuning the activation of CD4+ T cells, suggested that miR-31 may play critical roles in other physiological contexts where the CD4+ T cell homeostasis needs to be deliberately controlled.

Original languageEnglish (US)
Article number771279
JournalFrontiers in immunology
Volume12
DOIs
StatePublished - Nov 5 2021
Externally publishedYes

Keywords

  • CD4+ T cell
  • HIV-1
  • STAT1
  • T-bet
  • disease progression
  • miR-31

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Hsa-miR-31 Governs T-Cell Homeostasis in HIV Protection via IFN-γ-Stat1-T-Bet Axis'. Together they form a unique fingerprint.

Cite this