Galectin-3 promotes caspase-independent cell death of HIV-1-infected macrophages

FEBS J. 2017 Jan;284(1):97-113. doi: 10.1111/febs.13955. Epub 2016 Dec 15.


HIV-1-infected macrophages are a key contributor to the formation of a viral reservoir and new treatment strategies focus on eliminating this pool of virus. Galectin-3 is a potent apoptosis-inducing protein that regulates diverse cellular activities. In the present study, we investigated whether galectin-3 could induce cell death in HIV-1-infected macrophages using HIV-1-infected THP1 monocytes (THP1-MNs) and THP1-derived macrophages (THP1-MΦs) as in vitro cellular models. We found that THP1-MΦs were more resistant than the THP1-MNs to HIV-1 infection-induced death, and that HIV-1 infection of the THP1-MΦs increased expression of the anti-apoptotic proteins Mcl-1, Bcl-2 and Bcl-xL. Additionally, galectin-3 but not FasL, tumor necrosis factor (TNF)-related apoptosis-inducing ligand or TNF-α, could induce cell death in HIV-1-infected THP1-MΦs. A similar result was shown for primary human monocyte-derived macrophages. Galectin-3-induced cell death was also significantly increased in macrophages obtained from SIVmac251-infected macaques compared to that of macrophages from healthy macaques. Furthermore, galectin-3-induced cell death in HIV-1-infected THP1-MΦs was caspase independent. Interestingly, endonuclease G (Endo G) was increased in the nucleus and decreased in the cytoplasm of galectin-3-treated cells; thus, galectin-3-induced cell death in HIV-1-infected THP1-MΦs is most likely related to the translocation of Endo G from the cytoplasm to the nucleus. These findings suggest that galectin-3 may potentially aid in the eradication of HIV-1/SIV-infected macrophages.

Keywords: HIV-1; SIV; cell death; galectin-3; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Cell Death / drug effects
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Endodeoxyribonucleases / genetics*
  • Endodeoxyribonucleases / metabolism
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism
  • Galectin 3 / genetics
  • Galectin 3 / metabolism
  • Galectin 3 / pharmacology*
  • Gene Expression Regulation
  • HIV-1 / drug effects*
  • HIV-1 / growth & development
  • Humans
  • Macaca
  • Macrophages / drug effects*
  • Macrophages / pathology
  • Macrophages / virology
  • Monocytes / drug effects*
  • Monocytes / pathology
  • Monocytes / virology
  • Myeloid Cell Leukemia Sequence 1 Protein / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Protein Transport / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Simian Immunodeficiency Virus / drug effects
  • Simian Immunodeficiency Virus / growth & development
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism


  • BCL2 protein, human
  • BCL2L1 protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • Galectin 3
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factor-alpha
  • bcl-X Protein
  • Endodeoxyribonucleases
  • endonuclease G