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Cited by 79HIV Research and TreatmentCellular transport and secretionImmunotherapy and Immune Responses

CD169-Mediated Trafficking of HIV to Plasma Membrane Invaginations in Dendritic Cells Attenuates Efficacy of Anti-gp120 Broadly Neutralizing Antibodies

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Akiyama, Hisashi, Ramirez, Nora-Guadalupe Pina, Gudheti, Manasa V., Gummuluru, Suryaram·2015·PLOS Pathogens
DOI 10.1371/journal.ppat.1004751PMC PMC4356592
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Abstract

Myeloid dendritic cells (DCs) can capture HIV-1 via the receptor CD169/Siglec-1 that binds to the ganglioside, GM3, in the virus particle membrane. In turn, HIV-1 particles captured by CD169, an I-type lectin, whose expression on DCs is enhanced upon maturation with LPS, are protected from degradation in CD169+ virus-containing compartments (VCCs) and disseminated to CD4⁺ T cells, a mechanism of DC-mediated HIV-1 trans-infection. In this study, we describe the mechanism of VCC formation and its role in immune evasion mechanisms of HIV-1. We find HIV-1-induced formation of VCCs is restricted to myeloid cells, and that the cytoplasmic tail of CD169 is dispensable for HIV-1 trafficking and retention within VCCs and subsequent trans-infection to CD4⁺ T cells. Interestingly, introduction of a di-aromatic endocytic motif in the cytoplasmic tail of CD169 that results in endocytosis of HIV-1 particles, suppressed CD169-mediated HIV-1 trans-infection. Furthermore, super-resolution microscopy revealed close association of CD169 and HIV-1 particles in surface-accessible but deep plasma membrane invaginations. Intriguingly, HIV-1 particles in deep VCCs were inefficiently accessed by anti-gp120 broadly neutralizing antibodies, VRC01 and NIH45-46 G54W, and thus were less susceptible to neutralization. Our study suggests that HIV-1 capture by CD169 can provide virus evasion from both innate (phagocytosis) and adaptive immune responses.

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  • HIV-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 [88]

  • Endocytosis of HIV-1 viral particles from the VCC, induced by modification in the cytoplasmic domain of Siglec-1, significantly decreases trans-infection of T cells.

    “Furthermore, endocytosis of HIV-1 viral particles from the VCC, induced by a modification in the cytoplasmic domain of Siglec-1, significantly decreased the trans-infection of T cells [88].”

    From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [88]

  • 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 [88]

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Cited by

Sorted by citations

Authors
Akiyama, H., Ramirez, N.-G. P., Gudheti, M. V., & Gummuluru, S.
Affiliations
  • Boston University (US)
  • Bruker (United States) (US)
Corresponding author
Gummuluru, Suryaram
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2015-03-11
Volume
11
Issue
3
Pages
e1004751
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1004751
PMC
PMC4356592
OpenAlex
W1981160943
Cited by
79
References
5
Citations by year
2026: 3 · 2025: 9 · 2024: 3 · 2023: 3 · 2022: 9 · 2021: 7 · 2020: 5 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 8 · 2015: 4
FWCI
5.23
Type
journal article
Language
en
Update notices
correction (2015-05-07)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (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 Institutes of Health (183-H12-5C, gp120, AI064099)
  • National Institute of Allergy and Infectious Diseases (HIV-1 gp120, R01AI064099, 183-H12-5C, AI064099, HIV-1)
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 › Immunotherapy and Immune Responses
Keywords
HIV-1, myeloid dendritic cells, plasma membrane invaginations, CD4+ T cells, VRC01, GM3 ganglioside, endocytosis, immune evasion, phagocytosis
MeSH terms
Cell Membrane, Dendritic Cells, Electrophoresis, Polyacrylamide Gel, Humans, Microscopy, Electron, HIV-1, HIV Infections, HIV Envelope Protein gp120, Virus Integration, Immune Evasion, Antibodies, Neutralizing, Sialic Acid Binding Ig-like Lectin 1

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