title: 3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells.
abstract: The efficiency of HIV infection is greatly enhanced when the virus is delivered at conjugates between CD4+ T cells and virus-bearing antigen-presenting cells such as macrophages or dendritic cells via specialized structures known as virological synapses. Using ion abrasion SEM, electron tomography, and superresolution light microscopy, we have analyzed the spatial architecture of cell-cell contacts and distribution of HIV virions at virological synapses formed between mature dendritic cells and T cells. We demonstrate the striking envelopment of T cells by sheet-like membrane extensions derived from mature dendritic cells, resulting in a shielded region for formation of virological synapses. Within the synapse, filopodial extensions emanating from CD4+ T cells make contact with HIV virions sequestered deep within a 3D network of surface-accessible compartments in the dendritic cell. Viruses are detected at the membrane surfaces of both dendritic cells and T cells, but virions are not released passively at the synapse; instead, virus transfer requires the engagement of T-cell CD4 receptors. The relative seclusion of T cells from the extracellular milieu, the burial of the site of HIV transfer, and the receptor-dependent initiation of virion transfer by T cells highlight unique aspects of cell-cell HIV transmission.
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Felts
authors.forename: Kedar
authors.initials: K
authors.lastname: Narayan
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.forename: Dan
authors.initials: D
authors.lastname: Shi
authors.forename: Charles M
authors.initials: CM
authors.lastname: Trubey
authors.forename: Jing
authors.initials: J
authors.lastname: Fu
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hartnell
authors.forename: Gordon T
authors.initials: GT
authors.lastname: Ruthel
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Schneider
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.forename: Julian W
authors.initials: JW
authors.lastname: Bess
authors.forename: Sina
authors.initials: S
authors.lastname: Bavari
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Lowekamp
authors.forename: Donald
authors.initials: D
authors.lastname: Bliss
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Sriram
authors.initials: S
authors.lastname: Subramaniam
mesh_terms: D000938:Antigen-Presenting Cells / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D002450:Cell Communication; D003713:Dendritic Cells / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D006678:HIV / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D013601:T-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D014771:Virion / Q000502:physiology*