Cell-to-Cell Transfer of HIV-1 via Virological Synapses Leads to Endosomal Virion Maturation that Activates Viral Membrane Fusion
Open accessAbstract
HIV-1 can infect T cells by cell-free virus or by direct virion transfer between cells through cell contact-induced structures called virological synapses (VS). During VS-mediated infection, virions accumulate within target cell endosomes. We show that after crossing the VS, the transferred virus undergoes both maturation and viral membrane fusion. Following VS transfer, viral membrane fusion occurs with delayed kinetics and transferred virions display reduced sensitivity to patient antisera compared to mature, cell-free virus. Furthermore, particle fusion requires that the transferred virions undergo proteolytic maturation within acceptor cell endosomes, which occurs over several hours. Rapid, live cell confocal microscopy demonstrated that viral fusion can occur in compartments that have moved away from the VS. Thus, HIV particle maturation activates viral fusion in target CD4+ T cell endosomes following transfer across the VS and may represent a pathway by which HIV evades antibody neutralization.
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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 [49]
Fusogenic capacity of HIV-1 Env is activated during proteolytic maturation of viral particles.
“Moreover, the fusogenic capacity of Env is activated during the proteolytic maturation of viral particles [49,50].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [49]
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SARS-CoV-2 spreads through cell-to-cell transmission
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“Moreover, the fusogenic capacity of Env is activated during the proteolytic maturation of viral particles [49,50].”
Background
- Authors
- Dale, B. M., McNerney, G. P., Thompson, D. L., Hubner, W., de los Reyes, K., Chuang, F. Y. S., Huser, T., & Chen, B. K.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- University of California Davis Medical Center (US)
- Corresponding author
- Chen, Benjamin K.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2011-12
- Volume
- 10
- Issue
- 6
- Pages
- 551-562
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3278276
- OpenAlex
- W1964093787
- Cited by
- 133
- References
- 5
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 9 · 2017: 14 · 2016: 14 · 2015: 14 · 2014: 13 · 2013: 16 · 2012: 18
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 594 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- PUB – Publications at Bielefeld University (Bielefeld University) (submittedVersion)
- Publikationen an der Universität Bielefeld (Universität Bielefeld) (submittedVersion)
- Funders
- National Science Foundation
- Burroughs Wellcome Fund
- National Institutes of Health (1f32ai091426-01)
- National Institute on Drug Abuse (DP1DA028866)
- National Institute of Allergy and Infectious Diseases (1F32AI091426, F32 AI091426, AI074420, R01AI074420, T32AI007647)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- HIV-1, virological synapse, viral fusion, CD4+ T cells, proteolytic maturation, cell-free virus
- MeSH terms
- Cell Line, Humans, Endosomes, Synapses, Virion, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Virus Internalization
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