Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2019-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02457-19 |
| _version_ | 1818424685342228480 |
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| author | Maorong Xie Héloïse Leroy Rémi Mascarau Marie Woottum Maeva Dupont Camille Ciccone Alain Schmitt Brigitte Raynaud-Messina Christel Vérollet Jérôme Bouchet Lucie Bracq Serge Benichou |
| author_facet | Maorong Xie Héloïse Leroy Rémi Mascarau Marie Woottum Maeva Dupont Camille Ciccone Alain Schmitt Brigitte Raynaud-Messina Christel Vérollet Jérôme Bouchet Lucie Bracq Serge Benichou |
| author_sort | Maorong Xie |
| collection | DOAJ |
| description | 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. IMPORTANCE We demonstrate that HIV-1 uses a common two-step cell-to-cell fusion mechanism for massive virus transfer from infected T lymphocytes and dissemination to myeloid target cells, including dendritic cells and macrophages as well as osteoclasts. This cell-to-cell infection process bypasses the restriction imposed by the SAMHD1 host cell restriction factor for HIV-1 replication, leading to the formation of highly virus-productive multinucleated giant cells as observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients. Since myeloid cells are emerging as important target cells of HIV-1, these results contribute to a better understanding of the role of these myeloid cells in pathogenesis, including cell-associated virus sexual transmission, cell-to-cell virus spreading, and establishment of long-lived viral tissue reservoirs. |
| first_indexed | 2024-12-14T14:01:58Z |
| format | Article |
| id | doaj.art-55cea1056e1441178801c8008015ffd7 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T14:01:58Z |
| publishDate | 2019-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-55cea1056e1441178801c8008015ffd72022-12-21T22:58:42ZengAmerican Society for MicrobiologymBio2150-75112019-12-0110610.1128/mBio.02457-19Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 RestrictionMaorong Xie0Héloïse Leroy1Rémi Mascarau2Marie Woottum3Maeva Dupont4Camille Ciccone5Alain Schmitt6Brigitte Raynaud-Messina7Christel Vérollet8Jérôme Bouchet9Lucie Bracq10Serge Benichou11Inserm U1016, Institut Cochin, Paris, FranceInserm U1016, Institut Cochin, Paris, FranceInstitut de Pharmacologie et de Biologie Structurale, CNRS, Université Paul Sabatier, Toulouse, FranceInserm U1016, Institut Cochin, Paris, FranceInstitut de Pharmacologie et de Biologie Structurale, CNRS, Université Paul Sabatier, Toulouse, FranceInserm U1016, Institut Cochin, Paris, FranceInserm U1016, Institut Cochin, Paris, FranceInstitut de Pharmacologie et de Biologie Structurale, CNRS, Université Paul Sabatier, Toulouse, FranceInstitut de Pharmacologie et de Biologie Structurale, CNRS, Université Paul Sabatier, Toulouse, FranceInserm U1016, Institut Cochin, Paris, FranceInserm U1016, Institut Cochin, Paris, FranceInserm U1016, Institut Cochin, Paris, FranceABSTRACT 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. IMPORTANCE We demonstrate that HIV-1 uses a common two-step cell-to-cell fusion mechanism for massive virus transfer from infected T lymphocytes and dissemination to myeloid target cells, including dendritic cells and macrophages as well as osteoclasts. This cell-to-cell infection process bypasses the restriction imposed by the SAMHD1 host cell restriction factor for HIV-1 replication, leading to the formation of highly virus-productive multinucleated giant cells as observed in vivo in lymphoid and nonlymphoid tissues of HIV-1-infected patients. Since myeloid cells are emerging as important target cells of HIV-1, these results contribute to a better understanding of the role of these myeloid cells in pathogenesis, including cell-associated virus sexual transmission, cell-to-cell virus spreading, and establishment of long-lived viral tissue reservoirs.https://journals.asm.org/doi/10.1128/mBio.02457-19HIV-1SAMHD1cell fusionmyeloid cellsvirus spreading |
| spellingShingle | Maorong Xie Héloïse Leroy Rémi Mascarau Marie Woottum Maeva Dupont Camille Ciccone Alain Schmitt Brigitte Raynaud-Messina Christel Vérollet Jérôme Bouchet Lucie Bracq Serge Benichou Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction mBio HIV-1 SAMHD1 cell fusion myeloid cells virus spreading |
| title | Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction |
| title_full | Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction |
| title_fullStr | Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction |
| title_full_unstemmed | Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction |
| title_short | Cell-to-Cell Spreading of HIV-1 in Myeloid Target Cells Escapes SAMHD1 Restriction |
| title_sort | cell to cell spreading of hiv 1 in myeloid target cells escapes samhd1 restriction |
| topic | HIV-1 SAMHD1 cell fusion myeloid cells virus spreading |
| url | https://journals.asm.org/doi/10.1128/mBio.02457-19 |
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