Groppelli, E; Starling, S; Jolly, C; (2014) Contact-induced mitochondria polarization supports HIV-1 virological synapse formation. Journal of Virology , 89 (1) pp. 14-24. 10.1128/JVI.02425-14.

Preview	PDF (Legends to Movies S1 to S8) zjv999099878so1.pdf Download (62kB)
	QuickTime Movie (Movie S1 (Volume-rendered three-dimensional reconstruction of an HIV-1-infected CD4 T cell engaged with an uninfected target CD4 T cell.) ) zjv999099878sm2.mov Download (152kB)
	QuickTime Movie (Movie S2 (Live-cell imaging of mitochondrion recruitment to the contact zone formed between an HIV-1-infected Jurkat CD4 T cell and an uninfected target T cell [duration, 48 minutes].) ) zjv999099878sm3.mov Download (597kB)
	QuickTime Movie (Movie S3 (Live-cell imaging of mitochondrion recruitment to the contact zone formed between an HIV-1-infected Jurkat CD4 T cell and an uninfected target T cell [as described for Movie S2; duration, 34 minutes].) ) zjv999099878sm4.mov Download (231kB)
	QuickTime Movie (Movie S4 (Live-cell imaging of mitochondrion recruitment as described for Movie S2 except that primary CD4 T cells were infected with HIV-1 Gag-GFP reporter virus and mixed with autologous CD4 T cells [duration, 38 minutes].) ) zjv999099878sm5.mov Download (124kB)
	QuickTime Movie (ovie S5 (Live-cell imaging of mitochondrion recruitment as described for Movie S2 except that primary CD4 T cells were infected with HIV-1 Gag-GFP reporter virus and mixed with autologous CD4 T cells [as described for Movie S4; duration, 28 minutes].) ) zjv999099878sm6.mov Download (111kB)
	QuickTime Movie (Movie S6 (Live-cell imaging showing that transient contacts between HIV-1-infected T cells and target cells fail to induce polarization.) ) zjv999099878sm7.mov Download (657kB)
	QuickTime Movie (Movie S7 (Volume-rendered three-dimensional reconstruction of a polarized HIV-1-infected CD4 T cell treated with DMSO engaged with an uninfected target CD4 T cell.) ) zjv999099878sm8.mov Download (166kB)
	QuickTime Movie (Movie S8 (Volume-rendered three-dimensional reconstruction of a nonpolarized HIV-1-infected CD4 T cell pretreated with 50 µM Mdivi engaged with an uninfected target CD4 T cell.) ) zjv999099878sm9.mov Download (88kB)
	PDF (Article) 14.full.pdf Download (2MB)

Abstract

Rapid HIV-1 spread between CD4 T lymphocytes occurs at retrovirus-induced immune cell contacts called virological synapses (VS). VS are associated with striking T cell polarization and localized virus budding at the site of contact that facilitates cell-cell spread. In addition to this, spatial clustering of organelles including mitochondria to the contact zone has been previously shown. However, whether cell-cell contact specifically induces dynamic T cell remodeling during VS formation and what regulates this process remains unclear. Here we report that contact between an HIV-1 infected T cell and an uninfected target T cell specifically triggers polarization of mitochondria concomitant with recruitment of the major HIV-1 structural protein Gag to the site of cell-cell contact. Using fixed and live cell imaging we show that mitochondria and Gag polarization in HIV-1 infected T cells occurs within minutes of contact with target T cells, requires the formation of stable cell-cell contacts and is an active, calcium-dependent process. We also find that perturbation of mitochondria polarization impairs cell-cell spread of HIV-1 at the VS. Taken together these data suggest that HIV-1 infected T cells are able to sense and respond to contact with susceptible target cells and undergo dynamic cytoplasmic remodeling to create a synaptic environment that supports efficient HIV-1 VS formation between CD4 T lymphocytes.

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