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Cited by 181HIV Research and TreatmentImmunotherapy and Immune Responsesinterferon and immune responses

Interferon-Inducible Mechanism of Dendritic Cell-Mediated HIV-1 Dissemination Is Dependent on Siglec-1/CD169

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Puryear, Wendy Blay, Akiyama, Hisashi, Geer, Suzanne D., Ramirez, Nora P., Yu, Xinwei, Reinhard, Björn M., Gummuluru, Suryaram·2013·PLoS Pathogens
DOI 10.1371/journal.ppat.1003291PMC PMC3623718
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Abstract

Human immunodeficiency virus type 1 (HIV-1) interactions with myeloid dendritic cells (DCs) can result in virus dissemination to CD4⁺ T cells via a trans infection pathway dependent on virion incorporation of the host cell derived glycosphingolipid (GSL), GM3. The mechanism of DC-mediated trans infection is extremely efficacious and can result in infection of multiple CD4⁺ T cells as these cells make exploratory contacts on the DC surface. While it has long been appreciated that activation of DCs with ligands that induce type I IFN signaling pathway dramatically enhances DC-mediated T cell trans infection, the mechanism by which this occurs has remained unclear until now. Here, we demonstrate that the type I IFN-inducible Siglec-1, CD169, is the DC receptor that captures HIV in a GM3-dependent manner. Selective downregulation of CD169 expression, neutralizing CD169 function, or depletion of GSLs from virions, abrogated DC-mediated HIV-1 capture and trans infection, while exogenous expression of CD169 in receptor-naïve cells rescued GSL-dependent capture and trans infection. HIV-1 particles co-localized with CD169 on DC surface immediately following capture and subsequently within non-lysosomal compartments that redistributed to the DC--T cell infectious synapses upon initiation of T cell contact. Together, these findings describe a novel mechanism of pathogen parasitization of host encoded cellular recognition machinery (GM3--CD169 interaction) for DC-dependent HIV dissemination.

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Cited by

Sorted by citations

Authors
Puryear, W. B., Akiyama, H., Geer, S. D., Ramirez, N. P., Yu, X., Reinhard, B. M., & Gummuluru, S.
Affiliations
Boston University (US)
Corresponding author
Gummuluru, Suryaram
ORCID
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2013-04-11
Volume
9
Issue
4
Pages
e1003291
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1003291
PMC
PMC3623718
OpenAlex
W2044086145
Cited by
181
References
12
Citations by year
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FWCI
6.58
Type
journal article
Language
en
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
  • Yale University
  • Institut National de la Santé et de la Recherche Médicale
  • National Institutes of Health (183-H12-5C, gp120, AI064099, CA138509, AI007309)
  • National Cancer Institute (R01CA138509, CA138509)
  • National Institute of Allergy and Infectious Diseases (R01AI064099, AI064099, F32AI084558, T32AI007309)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
HIV-1, dendritic cells, CD169, Siglec-1, type I interferon, trans-infection, viral dissemination, CD4+ T cells, viral capture, myeloid dendritic cells
MeSH terms
Animals, Cell Line, Dendritic Cells, G(M3) Ganglioside, Humans, Signal Transduction, CD4-Positive T-Lymphocytes, HIV-1, Down-Regulation, HIV Infections, Interferon-alpha, RNA Interference, Mice, Rats, HEK293 Cells, Sialic Acid Binding Ig-like Lectin 1

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