title: HIV-1-Induced Small T Cell Syncytia Can Transfer Virus Particles to Target Cells through Transient Contacts.
abstract: HIV-1 Env mediates fusion of viral and target cell membranes, but it can also mediate fusion of infected (producer) and target cells, thus triggering the formation of multinucleated cells, so-called syncytia. Large, round, immobile syncytia are readily observable in cultures of HIV-1-infected T cells, but these fast growing "fusion sinks" are largely regarded as cell culture artifacts. In contrast, small HIV-1-induced syncytia were seen in the paracortex of peripheral lymph nodes and other secondary lymphoid tissue of HIV-1-positive individuals. Further, recent intravital imaging of lymph nodes in humanized mice early after their infection with HIV-1 demonstrated that a significant fraction of infected cells were highly mobile, small syncytia, suggesting that these entities contribute to virus dissemination. Here, we report that the formation of small, migratory syncytia, for which we provide further quantification in humanized mice, can be recapitulated in vitro if HIV-1-infected T cells are placed into 3D extracellular matrix (ECM) hydrogels rather than being kept in traditional suspension culture systems. Intriguingly, live-cell imaging in hydrogels revealed that these syncytia, similar to individual infected cells, can transiently interact with uninfected cells, leading to rapid virus transfer without cell-cell fusion. Infected cells were also observed to deposit large amounts of viral particles into the extracellular space. Altogether, these observations suggest the need to further evaluate the biological significance of small, T cell-based syncytia and to consider the possibility that these entities do indeed contribute to virus spread and pathogenesis.
authors.affiliation: Graduate Program in Cell and Molecular Biology, University of Vermont, Burlington, VT 05405, USA. msymeoni@uvm.edu.|Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA. msymeoni@uvm.edu.
authors.forename: Menelaos
authors.initials: M
authors.lastname: Symeonides
authors.affiliation: Departments of Immunology and Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada. thomas.murooka@umanitoba.ca.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Murooka
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA. lbellfy@uvm.edu.
authors.forename: Lauren N
authors.initials: LN
authors.lastname: Bellfy
authors.affiliation: Graduate Program in Cell and Molecular Biology, University of Vermont, Burlington, VT 05405, USA. royn@email.chop.edu.|Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA. royn@email.chop.edu.
authors.forename: Nathan H
authors.initials: NH
authors.lastname: Roy
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. tmempel@mgh.harvard.edu.
authors.forename: Thorsten R
authors.initials: TR
authors.lastname: Mempel
authors.affiliation: Graduate Program in Cell and Molecular Biology, University of Vermont, Burlington, VT 05405, USA. markus.thali@uvm.edu.|Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA. markus.thali@uvm.edu.
authors.forename: Markus
authors.initials: M
authors.lastname: Thali
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D015726:Giant Cells / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D020100:Hydrogels; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000821:virology*; D014771:Virion / Q000302:isolation & purification; D053586:Virus Internalization
chemical_list: D020100:Hydrogels
keywords: 3D culture; HIV; cell-cell fusion; humanized mouse; live cell imaging; syncytia