Zinc finger and interferon-stimulated genes play a vital role in TB-IRIS following HAART in AIDS

Per Med. 2018 Jul 1;15(4):251-269. doi: 10.2217/pme-2017-0084. Epub 2018 Jul 9.

Abstract

Aim: Co-infection in HIV-1 patients with Mycobacterium tuberculosis poses considerable risk of developing the immune reconstitution inflammatory syndrome (IRIS), especially upon the initiation of antiretroviral therapy (ART). Methodology & results: For transcriptomic analysis, peripheral blood mononuclear cells' whole gene expression was used from three patient groups: HIV+ (H), HIV-TB+ (HT), HIV-TB+ with IRIS (HTI). Pathway enrichment and functional analysis was performed before and after highly active ART. Genes in the interferon-stimulating and ZNF families maintained tight functional interaction and tilted the balance in favor of TB-IRIS.

Discussion & conclusion: The functional impairment of interaction between ZNF genes and interferon-stimulated genes, along with higher expression of S100A8/S100A9 genes possibly forms the genomic basis of TB-IRIS in a subset of HIV patients while on highly active ART.

Keywords: DEG; HAART; HIV; TB-IRIS; ZNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiretroviral Therapy, Highly Active
  • Calgranulin A / genetics
  • Calgranulin B / genetics
  • Coinfection / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks*
  • Genome-Wide Association Study
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / genetics*
  • Interferons / pharmacology
  • Interferons / therapeutic use
  • Sequence Analysis, RNA
  • Tuberculosis / genetics*
  • Zinc Fingers

Substances

  • Calgranulin A
  • Calgranulin B
  • S100A8 protein, human
  • S100A9 protein, human
  • Interferons