Galectin-9 is rapidly released during acute HIV-1 infection and remains sustained at high levels despite viral suppression even in elite controllers

AIDS Res Hum Retroviruses. 2014 Jul;30(7):654-64. doi: 10.1089/AID.2014.0004. Epub 2014 May 28.


Galectin-9 (Gal-9) is a β-galactosidase-binding lectin that promotes apoptosis, tissue inflammation, and T cell immune exhaustion, and alters HIV infection in part through engagement with the T cell immunoglobulin mucin domain-3 (Tim-3) receptor and protein disulfide isomerases (PDI). Gal-9 was initially thought to be an eosinophil attractant, but is now known to mediate multiple complex signaling events that affect T cells in both an immunosuppressive and inflammatory manner. To understand the kinetics of circulating Gal-9 levels during HIV infection we measured Gal-9 in plasma during HIV acquisition, in subjects with chronic HIV infection with differing virus control, and in uninfected individuals. During acute HIV infection, circulating Gal-9 was detected as early as 5 days after quantifiable HIV RNA and tracked plasma levels of interleukin (IL)-10, tumor necrosis factor (TNF)-α, and IL-1β. In chronic HIV infection, Gal-9 levels positively correlated with plasma HIV RNA levels (r=0.29; p=0.023), and remained significantly elevated during suppressive antiretroviral therapy (median: 225.3 pg/ml) and in elite controllers (263.3 pg/ml) compared to age-matched HIV-uninfected controls (54 pg/ml). Our findings identify Gal-9 as a novel component of the first wave of the cytokine storm in acute HIV infection that is sustained at elevated levels in virally suppressed subjects and suggest that Gal-9:Tim-3 crosstalk remains active in elite controllers and antiretroviral (ARV)-suppressed subjects, potentially contributing to ongoing inflammation and persistent T cell dysfunction.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Retroviral Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Galectins / blood
  • Galectins / immunology*
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1 / genetics
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Immune Tolerance / immunology
  • Interleukin-10 / blood
  • Interleukin-1beta / blood
  • Membrane Proteins / metabolism*
  • Protein Disulfide-Isomerases / metabolism
  • RNA, Viral / blood*
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / blood


  • Anti-Retroviral Agents
  • Galectins
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • IL10 protein, human
  • IL1B protein, human
  • Interleukin-1beta
  • LGALS9 protein, human
  • Membrane Proteins
  • RNA, Viral
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Protein Disulfide-Isomerases