Xie, M;
Leroy, H;
Mascarau, R;
Woottum, M;
Dupont, M;
Ciccone, C;
Schmitt, A;
... Benichou, S; + view all
(2019)
Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction.
mBio
, 10
(6)
, Article e02457-19. 10.1128/mbio.02457-19.
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Abstract
Dendritic cells (DCs) and macrophages as well as osteoclasts (OCs) are emerging as target cells of HIV-1 involved in virus transmission, dissemination, and establishment of persistent tissue virus reservoirs. While these myeloid cells are poorly infected by cell-free viruses because of the high expression levels of cellular restriction factors such as SAMHD1, we show here that HIV-1 uses a specific and common cell-to-cell fusion mechanism for virus transfer and dissemination from infected T lymphocytes to the target cells of the myeloid lineage, including immature DCs (iDCs), OCs, and macrophages, but not monocytes and mature DCs. The establishment of contacts with infected T cells leads to heterotypic cell fusion for the fast and massive transfer of viral material into OC and iDC targets, which subsequently triggers homotypic fusion with noninfected neighboring OCs and iDCs for virus dissemination. These two cell-to-cell fusion processes are not restricted by SAMHD1 and allow very efficient spreading of virus in myeloid cells, resulting in the formation of highly virus-productive multinucleated giant cells. These results reveal the cellular mechanism for SAMHD1-independent cell-to-cell spreading of HIV-1 in myeloid cell targets through the formation of the infected multinucleated giant cells observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients.
| Type: | Article |
|---|---|
| Title: | Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1128/mbio.02457-19 |
| Publisher version: | https://doi.org/10.1128/mBio.02457-19 |
| Language: | English |
| Additional information: | Copyright © 2019 Xie et al. This is an openaccess article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | HIV-1, SAMHD1, cell fusion, myeloid cells, virus spreading |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10087592 |
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