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

T cell-macrophage fusion triggers multinucleated giant cell formation for HIV-1 spreading.
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Bracq L, Xie M, Lambelé M, Vu LT, Matz J, Schmitt A, Delon J, Zhou P, Randriamampita C, Bouchet J, Benichou S,


Bracq L, Xie M, Lambelé M, Vu LT, Matz J, Schmitt A, Delon J, Zhou P, Randriamampita C, Bouchet J, Benichou S, (click to view)

Bracq L, Xie M, Lambelé M, Vu LT, Matz J, Schmitt A, Delon J, Zhou P, Randriamampita C, Bouchet J, Benichou S,

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Journal of virology 2017 10 04() pii 10.1128/JVI.01237-17

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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