title: Siglec-1 is a novel dendritic cell receptor that mediates HIV-1 trans-infection through recognition of viral membrane gangliosides.
abstract: Dendritic cells (DCs) are essential antigen-presenting cells for the induction of immunity against pathogens. However, HIV-1 spread is strongly enhanced in clusters of DCs and CD4(+) T cells. Uninfected DCs capture HIV-1 and mediate viral transfer to bystander CD4(+) T cells through a process termed trans-infection. Initial studies identified the C-type lectin DC-SIGN as the HIV-1 binding factor on DCs, which interacts with the viral envelope glycoproteins. Upon DC maturation, however, DC-SIGN is down-regulated, while HIV-1 capture and trans-infection is strongly enhanced via a glycoprotein-independent capture pathway that recognizes sialyllactose-containing membrane gangliosides. Here we show that the sialic acid-binding Ig-like lectin 1 (Siglec-1, CD169), which is highly expressed on mature DCs, specifically binds HIV-1 and vesicles carrying sialyllactose. Furthermore, Siglec-1 is essential for trans-infection by mature DCs. These findings identify Siglec-1 as a key factor for HIV-1 spread via infectious DC/T-cell synapses, highlighting a novel mechanism that mediates HIV-1 dissemination in activated tissues.
authors.affiliation: AIDS Research Institute IrsiCaixa, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. nizquierdo@irsicaixa.es
authors.forename: Nuria
authors.initials: N
authors.lastname: Izquierdo-Useros
authors.forename: Maier
authors.initials: M
authors.lastname: Lorizate
authors.forename: Maria C
authors.initials: MC
authors.lastname: Puertas
authors.forename: Maria T
authors.initials: MT
authors.lastname: Rodriguez-Plata
authors.forename: Nadine
authors.initials: N
authors.lastname: Zangger
authors.forename: Elina
authors.initials: E
authors.lastname: Erikson
authors.forename: Maria
authors.initials: M
authors.lastname: Pino
authors.forename: Itziar
authors.initials: I
authors.lastname: Erkizia
authors.forename: Bärbel
authors.initials: B
authors.lastname: Glass
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Keppler
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Kräusslich
authors.forename: Javier
authors.initials: J
authors.lastname: Martinez-Picado
mesh_terms: D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D055354:Exosomes / Q000187:drug effects / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D057809:HEK293 Cells; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D054992:Immunological Synapses / Q000187:drug effects; D008051:Lipid Bilayers / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008081:Liposomes / Q000378:metabolism; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014771:Virion / Q000187:drug effects / Q000378:metabolism
chemical_list: D005732:Gangliosides; D008051:Lipid Bilayers; D008070:Lipopolysaccharides; D008081:Liposomes; D063267:Sialic Acid Binding Ig-like Lectin 1