HIV Traffics through a Specialized, Surface-Accessible Intracellular Compartment during trans-Infection of T Cells by Mature Dendritic Cells
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In vitro, dendritic cells (DCs) bind and transfer intact, infectious HIV to CD4 T cells without first becoming infected, a process known as trans-infection. trans-infection is accomplished by recruitment of HIV and its receptors to the site of DC-T cell contact and transfer of virions at a structure known as the infectious synapse. In this study, we used fluorescent microscopy to track individual HIV particles trafficking in DCs during virus uptake and trans-infection. Mature DCs rapidly concentrated HIV into an apparently intracellular compartment that lacked markers characteristic of early endosomes, lysosomes, or antigen-processing vesicles. Live cell microscopy demonstrated that the HIV-containing compartment was rapidly polarized toward the infectious synapse after contact with a T cell; however, the bulk of the concentrated virus remained in the DCs after T cell engagement. Individual virions were observed emerging from the compartment and fusing with the T cell membrane at the infectious synapse. The compartmentalized HIV, although engulfed by the cytoplasm, was fully accessible to HIV envelope-specific inhibitors and other membrane-impermeable probes that were delivered to the cell surface. These results demonstrate that HIV resides in an invaginated domain within DCs that is both contiguous with the plasma membrane and distinct from endocytic vesicles. We conclude that HIV virions are routed through this specialized compartment, which allows individual particles to be delivered to T cells during trans-infection.
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HIV-1 virions accumulate in invaginations of the plasma membrane of LPS-activated and myeloid DCs; upon DC-T cell contact, VCCs polarize to the IS, ensuring delivery of viral particles for transmission.
“The VCC transmission model is based on the results of fluorescence microscopy, which revealed the accumulation of HIV-1 virions in the invaginations of the plasma membrane of lipopolysaccharide-activated and myeloid DCs. Upon the contact of DCs with T cells, VCCs were polarized to the IS, ensuring the delivery of viral particles for transmission [96].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [96]
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- Authors
- Yu, H. J., Reuter, M. A., & McDonald, D.
- Affiliations
- Case Western Reserve University (US)
- Corresponding author
- McDonald, David
- ORCID
- Reuter, Morgan A.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-08-22
- Volume
- 4
- Issue
- 8
- Pages
- e1000134
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC2515344
- OpenAlex
- W2069818169
- Cited by
- 193
- References
- 68
- Citations by year
- 2026: 2 · 2025: 4 · 2023: 4 · 2022: 10 · 2021: 10 · 2020: 6 · 2019: 13 · 2018: 12 · 2017: 12 · 2016: 7 · 2015: 8 · 2014: 16 · 2013: 16 · 2012: 22
- FWCI
- 5.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- OhioLink ETD Center (Ohio Library and Information Network) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- Center for AIDS Research, University of Washington
- National Institute of General Medical Sciences (T32GM008056, T32-GM-08056)
- National Institute of Allergy and Infectious Diseases (R21AI073242)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- dendritic cells, CD4+ T cells, intracellular compartments, viral uptake, membrane fusion
- MeSH terms
- Cell Communication, Dendritic Cells, HIV, Humans, Endosomes, Virion, CD4-Positive T-Lymphocytes, HIV Infections, Jurkat Cells
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