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Viruses 2015, 7(12), 6590-6603; doi:10.3390/v7122959

HIV-1-Induced Small T Cell Syncytia Can Transfer Virus Particles to Target Cells through Transient Contacts

1
Graduate Program in Cell and Molecular Biology, University of Vermont, Burlington, VT 05405, USA
2
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA
3
Departments of Immunology and Medical Microbiology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada
4
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
Current address: Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Received: 30 July 2015 / Revised: 27 November 2015 / Accepted: 2 December 2015 / Published: 12 December 2015
(This article belongs to the Section Animal Viruses)
View Full-Text   |   Download PDF [8376 KB, uploaded 17 December 2015]   |  

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. View Full-Text
Keywords: HIV; cell-cell fusion; syncytia; humanized mouse; 3D culture; live cell imaging HIV; cell-cell fusion; syncytia; humanized mouse; 3D culture; live cell imaging
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Symeonides, M.; Murooka, T.T.; Bellfy, L.N.; Roy, N.H.; Mempel, T.R.; Thali, M. HIV-1-Induced Small T Cell Syncytia Can Transfer Virus Particles to Target Cells through Transient Contacts. Viruses 2015, 7, 6590-6603.

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