Galectin-3 promotes HIV-1 budding via association with Alix and Gag p6

Sheng Fan Wang, Ching Han Tsao, Yu Ting Lin, Daniel K. Hsu, Meng Lin Chiang, Chia Hui Lo, Fan Ching Chien, Peilin Chen, Yi Ming Arthur Chen, Huan Yuan Chen, Fu Tong Liu

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

Galectin-3 has been reported to regulate the functions of a number of immune cell types. We previously reported that galectin-3 is translocated to immunological synapses in T cells upon T-cell receptor engagement, where it associates with ALG-2-interacting protein X (Alix). Alix is known to coordinate with the endosomal sorting complex required for transport (ESCRT) to promote human immunodeficiency virus (HIV)-1 virion release. We hypothesized that galectin-3 plays a role in HIV-1 viral budding. Cotransfection of cells of the Jurkat T line with galectin-3 and HIV-1 plasmids resulted in increased HIV-1 budding, and suppression of galectin-3 expression by RNAi in Hut78 and primary CD4+ T cells led to reduced HIV-1 budding. We used immunofluorescence microscopy to observe the partial colocalization of galectin-3, Alix and Gag in HIV-1-infected cells. Results from co-immunoprecipitation experiments indicate that galectin-3 expression promotes Alix-Gag p6 association, whereas the results of Alix knockdown suggest that galectin-3 promotes HIV-1 budding through Alix. HIV-1 particles released from galectin-3-expressing cells acquire the galectin-3 protein in an Alix-dependent manner, with proteins primarily residing inside the virions. We also found that the galectin-3 N-terminal domain interacts with the proline-rich region of Alix. Collectively, these results suggest that endogenous galectin-3 facilitates HIV-1 budding by promoting the Alix-Gag p6 association.

Original languageEnglish
Pages (from-to)1022-1035
Number of pages14
JournalGlycobiology
Volume24
Issue number11
DOIs
Publication statusPublished - Nov 1 2014
Externally publishedYes

Keywords

  • Alix
  • galectin-3
  • HIV-1
  • viral budding

ASJC Scopus subject areas

  • Biochemistry

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