Quantitative 3D Video Microscopy of HIV Transfer Across T Cell Virological Synapses
Open accessAbstract
The spread of HIV between immune cells is greatly enhanced by cell-cell adhesions called virological synapses, although the underlying mechanisms have been unclear. With use of an infectious, fluorescent clone of HIV, we tracked the movement of Gag in live CD4 T cells and captured the direct translocation of HIV across the virological synapse. Quantitative, high-speed three-dimensional (3D) video microscopy revealed the rapid formation of micrometer-sized "buttons" containing oligomerized viral Gag protein. Electron microscopy showed that these buttons were packed with budding viral crescents. Viral transfer events were observed to form virus-laden internal compartments within target cells. Continuous time-lapse monitoring showed preferential infection through synapses. Thus, HIV dissemination may be enhanced by virological synapse-mediated cell adhesion coupled to viral endocytosis.
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According to the Chen et al. model, HIV-1 viral particles are internalized from the synaptic cleft into early endosomes of the target cell, where they undergo proteolytic maturation followed by fusion with the endosomal membrane.
“According to the model of Chen et al. [29], HIV-1 viral particles are internalized from the synaptic cleft into the early endosomes of the target cell, where they undergo proteolytic maturation followed by fusion with the endosomal membrane [49,51,52].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [52]
The paper reports that HIV crosses virological synapses into vesicular compartments in recipient cells. It does not identify those compartments as early endosomes or show proteolytic maturation followed by fusion with the endosomal membrane; its discussion presents fusion within a target-cell compartment as a possibility, not an observed sequence. The relevant passages are indexed under Abstract; no page is supplied. (LLM, conf=0.88)
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Cites
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Virus cell-to-cell transmission
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Molecular determinants that regulate plasma membrane association of HIV-1 Gag
Chukkapalli, V., & Ono, A. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.04.015 · Cited by 129 · see citing works
HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread
Kalinichenko, S., Komkov, D., & Mazurov, D. (2022) · Viruses · doi:10.3390/v14010152 · Cited by 68 · see citing works
“[29], HIV-1 viral particles are internalized from the synaptic cleft into the early endosomes of the target cell, where they undergo proteolytic maturation followed by fusion with the endosomal membrane [49,51,52].”
Background
- Authors
- Hübner, W., McNerney, G. P., Chen, P., Dale, B. M., Gordon, R. E., Chuang, F. Y. S., Li, X.-D., Asmuth, D. M., Huser, T., & Chen, B. K.
- Affiliations
- Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
- University of California Davis Medical Center (US)
- Corresponding author
- Chen, Benjamin K.
- Venue
- Science
- Published
- 2009-03-27
- Volume
- 323
- Issue
- 5922
- Pages
- 1743-1747
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2756521
- OpenAlex
- W2030541908
- Cited by
- 486
- References
- 1
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 13 · 2023: 22 · 2022: 37 · 2021: 27 · 2020: 30 · 2019: 25 · 2018: 23 · 2017: 25 · 2016: 27 · 2015: 23 · 2014: 32 · 2013: 37 · 2012: 48
- FWCI
- 17.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PUB – Publications at Bielefeld University (Bielefeld University) (submittedVersion)
- Publikationen an der Universität Bielefeld (Universität Bielefeld) (submittedVersion)
- Funders
- National Institutes of Health (1s10rr009145-01)
- U.S. Public Health Service (ULRR024146)
- National Institute on Drug Abuse (DP1DA028866)
- National Cancer Institute (R24CA095823)
- National Institute of Allergy and Infectious Diseases (R01AI074420)
- National Center for Research Resources (S10 RR0 9145-01)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- HIV, virological synapse, cell-to-cell transmission, Gag protein, CD4+ T cells, viral budding, viral endocytosis, live-cell imaging, cell adhesion
- MeSH terms
- Cell Adhesion, Endocytosis, HIV, Humans, Recombinant Fusion Proteins, CD4-Positive T-Lymphocytes, Cytochalasin D, Microscopy, Confocal, Microscopy, Video, Coculture Techniques, Jurkat Cells, Receptors, CCR5, Receptors, CXCR4, Imaging, Three-Dimensional, Microscopy, Electron, Transmission, Virus Internalization, gag Gene Products, Human Immunodeficiency Virus
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