Journal
GLYCOBIOLOGY
Volume 32, Issue 9, Pages 760-777Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/glycob/cwac040
Keywords
CD4 T cell; galectin-3; HIV-1; lipid raft; virological synapse
Categories
Funding
- Ministry of Science and Technology, R.O.C. [MOST 106-2321-B-037-001, MOST 105-2911-1-037-504, MOST 106-0210-0115-02]
- Kaohsiung Medical University Research Foundation [105KMUOR05]
Ask authors/readers for more resources
The study reveals that GAL3 promotes cell-to-cell transmission of HIV-1 in CD4 T cells by regulating lipid raft components. GAL3 is co-transferred with Gag to recipient cells and facilitates viral synapse formation at the cell-cell interface.
Galectin-3 (GAL3) is a beta-galactoside-binding lectin expressed in CD4 T cells infected with human immunodeficiency virus-1 (HIV-1). GAL3 promotes HIV-1 budding by associating with ALIX and Gag p6. GAL3 has been shown to localize in membrane lipid rafts in dendritic cells and positively regulate cell migration. HIV-1 spreads between T cells by forming supramolecular structures (virological synapses [VSs]), whose integrity depends on lipid rafts. Here, we addressed the potential role of GAL3 in cell-to-cell transmission of HIV-1 in CD4 T cells. GAL3 expressed in donor cells was more important for facilitating HIV-1 cell-to-cell transfer than GAL3 expressed in target cells. GAL3 was found to be co-transferred with Gag from HIV-1-positive donor to HIV-1-negative target T cells. HIV-1 infection induced translocation of GAL3 together with Gag to the cell-cell interfaces and colocalize with GM1, where GAL3 facilitated VS formation. GAL3 regulated the coordinated transfer of Gag and flotillin-1 into plasma membrane fractions. Finally, depletion of GAL3 reduced the cholesterol levels in membrane lipid rafts in CD4 T cells. These findings provide evidence that endogenous GAL3 stimulates lipid raft components and facilitates intercellular HIV-1 transfer among CD4 T cells, offering another pathway by which GAL3 regulates HIV-1 infection. These findings may inform the treatment of HIV-1 infection based on targeting GAL3 to modulate lipid rafts.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available