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Updated: Jun 24, 2026

Imaging of HIV-1 Envelope-induced Virological Synapse and Signaling on Synthetic Lipid Bilayers
Published on: March 8, 2012
Simultaneous cell-to-cell transmission of human immunodeficiency virus to multiple targets through polysynapses
Dominika Rudnicka1, Jérôme Feldmann, Françoise Porrot
1Department of Virology, Virus and Immunity Unit, Institut Pasteur, URA CNRS 3015, Paris Cedex 15, France.
Insights
Human immunodeficiency virus type 1 (HIV-1) spreads efficiently via cell-to-cell contacts, including newly identified "polysynapses." These structures facilitate rapid viral growth and immune evasion in infected individuals.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) spreads between cells through various contact structures.
- Understanding these transmission routes is crucial for controlling viral spread and immune escape.
Purpose of the Study:
- To quantify and characterize cell-to-cell contact modes for HIV-1 propagation in lymphocytes.
- To investigate the role of novel structures called polysynapses in viral transmission.
Main Methods:
- Quantification and characterization of cell-to-cell contacts in lymphocytes.
- Analysis of HIV Gag protein organization and colocalization with cellular markers at contact sites.
- Investigation of the role of LFA-1 adhesion molecule in polysynapse formation.
Main Results:
- Viral transmission occurs predominantly through virological synapses (VS) and polysynapses.
- Polysynapses are rosette-like structures enabling simultaneous HIV clustering and transfer to multiple cells.
- HIV Gag proteins form ring-like structures at intercellular contacts, independent of the microtubule organizing center.
- LFA-1 enhances polysynapse formation, facilitating viral replication.
Conclusions:
- Polysynapses represent an underestimated mode of HIV-1 transfer.
- These structures can promote exponential viral growth and immune system evasion in infected individuals.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) efficiently propagates through cell-to-cell contacts, which include virological synapses (VS), filopodia, and nanotubes. Here, we quantified and characterized further these diverse modes of contact in lymphocytes. We report that viral transmission mainly occurs across VS and through "polysynapses," a rosette-like structure formed between one infected cell and multiple adjacent recipients. Polysynapses are characterized by simultaneous HIV clustering and transfer at multiple membrane regions. HIV Gag proteins often adopt a ring-like supramolecular organization at sites of intercellular contacts and colocalize with CD63 tetraspanin and raft components GM1, Thy-1, and CD59. In donor cells engaged in polysynapses, there is no preferential accumulation of Gag proteins at contact sites facing the microtubule organizing center. The LFA-1 adhesion molecule, known to facilitate viral replication, enhances formation of polysynapses. Altogether, our results reveal an underestimated mode of viral transfer through polysynapses. In HIV-infected individuals, these structures, by promoting concomitant infection of multiple targets in the vicinity of infected cells, may facilitate exponential viral growth and escape from immune responses.
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