MicroRNA-155 Reinforces HIV Latency

J Biol Chem. 2015 May 29;290(22):13736-48. doi: 10.1074/jbc.M115.641837. Epub 2015 Apr 14.


The presence of a small number of infected but transcriptionally dormant cells currently thwarts a cure for the more than 35 million individuals infected with HIV. Reactivation of these latently infected cells may result in three fates: 1) cell death due to a viral cytopathic effect, 2) cell death due to immune clearance, or 3) a retreat into latency. Uncovering the dynamics of HIV gene expression and silencing in the latent reservoir will be crucial for developing an HIV-1 cure. Here we identify and characterize an intracellular circuit involving TRIM32, an HIV activator, and miR-155, a microRNA that may promote a return to latency in these transiently activated reservoir cells. Notably, we demonstrate that TRIM32, an E3 ubiquitin ligase, promotes reactivation from latency by directly modifying IκBα, leading to a novel mechanism of NF-κB induction not involving IκB kinase activation.

Keywords: HIV-1 latency; IκBα; NF-kappa B (NF-KB); TRIM32; microRNA (miRNA); molecular biology; viral transcription; virology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions
  • Amino Acid Motifs
  • Base Sequence
  • CD4-Positive T-Lymphocytes / virology
  • Cell Death
  • Gene Silencing
  • Genes, Reporter
  • HIV-1 / physiology*
  • Humans
  • I-kappa B Proteins / metabolism
  • Lentivirus / metabolism
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / metabolism*
  • Tripartite Motif Proteins
  • Ubiquitin / chemistry
  • Ubiquitin-Protein Ligases / metabolism
  • Virus Latency*
  • Virus Replication


  • 3' Untranslated Regions
  • I-kappa B Proteins
  • MIRN155 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • NFKBIA protein, human
  • Transcription Factors
  • Tripartite Motif Proteins
  • Ubiquitin
  • NF-KappaB Inhibitor alpha
  • TRIM25 protein, human
  • TRIM32 protein, human
  • Ubiquitin-Protein Ligases