title: Siglec-1 initiates formation of the virus-containing compartment and enhances macrophage-to-T cell transmission of HIV-1.
abstract: 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.
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Jason E
authors.identifier: 0000-0002-1649-9008
authors.initials: JE
authors.lastname: Hammonds
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Neal
authors.initials: N
authors.lastname: Beeman
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Lingmei
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Sarah
authors.identifier: 0000-0002-0401-6451
authors.initials: S
authors.lastname: Takushi
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Ashwanth C
authors.identifier: 0000-0002-8663-2038
authors.initials: AC
authors.lastname: Francis
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Jaang-Jiun
authors.identifier: 0000-0003-0732-465X
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Melikyan
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Paul
authors.identifier: 0000-0001-5393-9511
authors.initials: P
authors.lastname: Spearman
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007181:Inclusion Bodies, Viral / Q000648:ultrastructure; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism*; D059008:Time-Lapse Imaging; D014771:Virion / Q000472:pathogenicity
chemical_list: C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1