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J Virol. 2017 Oct 4. pii: JVI.01237-17. doi: 10.1128/JVI.01237-17. [Epub ahead of print]

T cell-macrophage fusion triggers multinucleated giant cell formation for HIV-1 spreading.

Bracq L1,2,3,4,5, Xie M1,2,3,5, Lambelé M1,2,3,5, Vu LT1,2,3,5, Matz J1,2,3, Schmitt A1,2,3, Delon J1,2,3, Zhou P4,5, Randriamampita C1,2,3, Bouchet J6,2,3,5, Benichou S6,2,3,5.

Author information

1
Inserm U1016, Institut Cochin, Paris, France.
2
CNRS, UMR8104, Paris, France.
3
Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France.
4
Institut Pasteur Shanghai-Chinese Academy of Sciences, Shanghai, China.
5
International Associated Laboratory (LIA VirHost), CNRS, Université Paris-Descartes, and Institut Pasteur Shanghai-Chinese Academy of Sciences.
6
Inserm U1016, Institut Cochin, Paris, France serge.benichou@inserm.fr jerome.bouchet@inserm.fr.

Abstract

HIV-1-infected macrophages participate in virus dissemination and establishment of virus reservoirs in host tissues, but the mechanisms for virus cell-to-cell transfer to macrophages remain unknown. Here, we reveal the mechanisms for cell-to-cell transfer from infected T cells to macrophages and virus spreading between macrophages. We show that contacts between infected T lymphocytes and macrophages lead to cell fusion for fast and massive transfer of CCR5-tropic viruses to macrophages. Through the merge of viral material between T cells and macrophages, these newly formed lymphocyte/macrophage fused cells acquire the ability to fuse with neighboring non-infected macrophages. Together, these two-step envelope-dependent cell fusion processes lead to the formation of highly virus-productive multinucleated giant cells reminiscent of the infected multinucleated giant macrophages detected in HIV-1-infected patients and SIV-infected macaques. These mechanisms represent an original mode of virus transmission for viral spreading and a new model for the formation of macrophage virus reservoirs during infection.IMPORTANCE We reveal a very efficient mechanism involved in cell-to-cell transfer from infected T cells to macrophages and subsequent virus spreading between macrophages by a two-step cell fusion process. Infected T cells first establish contacts and fuse with macrophage targets. The newly formed lymphocyte/macrophage fused cells then acquire the ability to fuse with surrounding uninfected macrophages leading to the formation of infected multinucleated giant cells that can survive for a long time as evidenced in vivo in lymphoid organs and the central nervous system. This route of infection may be a major determinant for virus dissemination and the formation of macrophage virus reservoirs in host tissues during HIV-1 infection.

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