Siglec-1 initiates formation of the virus-containing compartment and enhances macrophage-to-T cell transmission of HIV-1
Open accessAbstract
HIV-1 particles assemble and bud from the plasma membrane of infected T lymphocytes. Infected macrophages, in contrast, accumulate particles within an apparent intracellular compartment known as the virus-containing compartment or VCC. Many aspects of the formation and function of the VCC remain unclear. Here we demonstrate that VCC formation does not actually require infection of the macrophage, but can be reproduced through the exogenous addition of non-infectious virus-like particles or infectious virions to macrophage cultures. Particles were captured by Siglec-1, a prominent cell surface lectin that attaches to gangliosides on the lipid envelope of the virus. VCCs formed within infected macrophages were readily targeted by the addition of ganglioside-containing virus-like particles to the extracellular media. Depletion of Siglec-1 from the macrophage or depletion of gangliosides from viral particles prevented particle uptake into the VCC and resulted in substantial reductions of VCC volume. Furthermore, Siglec-1-mediated virion capture and subsequent VCC formation was required for efficient trans-infection of autologous T cells. Our results help to define the nature of this intracellular compartment, arguing that it is a compartment formed by particle uptake from the periphery, and that this compartment can readily transmit virus to target T lymphocytes. Inhibiting or eliminating the VCC may be an important component of strategies to reduce HIV transmission and to eradicate HIV reservoirs.
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HIV-1 viral particles are translocated from the VCC to the IS for transmission.
“Then, HIV-1 viral particles are translocated from the VCC to the IS for transmission.”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [85]
The Results section on trans-infection says virions retained in the VCC can subsequently contribute to transmission to T cells. The Discussion also refers to subsequent transmission at a virologic synapse, but it does not establish the claimed translocation of particles from the VCC to the IS. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHIV-1 viral particles in complex with Siglec-1 accumulate in VCCs, where they are protected from lysosomal degradation and neutralizing antibodies.
“In complex with Siglec-1, HIV-1 viral particles accumulate in deep invaginations of the plasma membrane, known as virus-containing compartments (VCCs), where they are protected from lysosomal degradation and neutralizing antibodies [85,88].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [85]
The Results (no page number provided) show that HIV-1 particles and Siglec-1 colocalize in macrophage VCCs. The Introduction describes VCCs as plasma-membrane-connected and non-acidic, with limited antibody accessibility, but cautions that antibody protection may be incomplete. Our copy does not establish protection from lysosomal degradation, so the claim overstates what this paper supports. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCD169/Siglec-1 mediates uptake and transmission of HIV-1.
“Another molecule that mediates the uptake and transmission of HIV-1 is the type I lectin receptor CD169/sialic acid-binding immunoglobulin-type lectin 1 (Siglec-1).”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [85]
Siglec-1 is expressed on activated mature DCs and macrophages and binds to GM3 ganglioside in the HIV-1 viral envelope.
“This receptor is expressed on the surface of activated mature DCs and macrophages, and binds to the GM3 ganglioside in the HIV-1 viral envelope [85,86,87].”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [85]
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Cites
Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors
Gomez Perdiguero, E., Klapproth, K., Schulz, C., Busch, K., Azzoni, E., Crozet, L., Garner, H., Trouillet, C., de Bruijn, M. F., Geissmann, F., et al. (2015) · Nature · doi:10.1038/nature13989 · Cited by 2,339 · cited 1× · see citing works
“Macrophages are present throughout every organ of the human body, and tissue-resident macrophages may be extremely long-lived, having been derived from progenitor cells during embryogenesis rather than being replaced at short intervals from circulating monocytes [4].”
Izquierdo-Useros, N., Lorizate, M., Puertas, M. C., Rodriguez-Plata, M. T., Zangger, N., Erikson, E., Pino, M., Erkizia, I., Glass, B., Clotet, B., et al. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001448 · Cited by 244 · cited 5× · see citing works
“Siglec-1 on the surface of DCs is capable of capturing HIV-1 in a glycosphingolipid-dependent manner [19, 20, 26].”
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Sorted by citations
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
“In complex with Siglec-1, HIV-1 viral particles accumulate in deep invaginations of the plasma membrane, known as viruscontaining compartments (VCCs), where they are protected from lysosomal degradation and neutralizing antibodies [85,88].”
BackgroundViral and host factors regulating HIV-1 envelope protein trafficking and particle incorporation
Anokhin, B., & Spearman, P. (2022) · Viruses · doi:10.3390/v14081729 · Cited by 21 · see citing works
Self-citation
- Authors
- Hammonds, J. E., Beeman, N., Ding, L., Takushi, S., Francis, A. C., Wang, J.-J., Melikyan, G. B., & Spearman, P.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Emory University (US)
- Corresponding author
- Spearman, Paul
- ORCID
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-01-27
- Volume
- 13
- Issue
- 1
- Pages
- e1006181
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC5298340
- OpenAlex
- W2580578756
- Cited by
- 110
- References
- 2
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 9 · 2023: 14 · 2022: 13 · 2021: 10 · 2020: 13 · 2019: 14 · 2018: 5 · 2017: 11
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Update notices
- new_version (2017-02-08)
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institute of Allergy and Infectious Diseases (AI058858)
- 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
- Siglec-1, HIV-1, macrophages, trans-infection, T cell infection, gangliosides, virus-like particles, cell surface lectins, HIV reservoir, virus transmission
- MeSH terms
- Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Inclusion Bodies, Viral, Macrophages, Microscopy, Fluorescence, Virion, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Microscopy, Electron, Transmission, Time-Lapse Imaging, Sialic Acid Binding Ig-like Lectin 1
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