title: Three-dimensional imaging of HIV-1 virological synapses reveals membrane architectures involved in virus transmission.
abstract: HIV transmission efficiency is greatly increased when viruses are transmitted at virological synapses formed between infected and uninfected cells. We have previously shown that virological synapses formed between HIV-pulsed mature dendritic cells (DCs) and uninfected T cells contain interdigitated membrane surfaces, with T cell filopodia extending toward virions sequestered deep inside invaginations formed on the DC membrane. To explore membrane structural changes relevant to HIV transmission across other types of intercellular conjugates, we used a combination of light and focused ion beam scanning electron microscopy (FIB-SEM) to determine the three-dimensional (3D) architectures of contact regions between HIV-1-infected CD4(+) T cells and either uninfected human CD4(+) T cells or human fetal astrocytes. We present evidence that in each case, membrane extensions that originate from the uninfected cells, either as membrane sheets or filopodial bridges, are present and may be involved in HIV transmission from infected to uninfected cells. We show that individual virions are distributed along the length of astrocyte filopodia, suggesting that virus transfer to the astrocytes is mediated, at least in part, by processes originating from the astrocyte itself. Mechanisms that selectively disrupt the polarization and formation of such membrane extensions could thus represent a possible target for reducing viral spread.
  
  
  OBJECTIVE
  Our findings lead to new insights into unique aspects of HIV transmission in the brain and at T cell-T cell synapses, which are thought to be a predominant mode of rapid HIV transmission early in the infection process.
authors: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Thao
authors: T
authors: Do
authors: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Gavin
authors: G
authors: Murphy
authors: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Lesley A
authors: LA
authors: Earl
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors: Gregory Q
authors: GQ
authors: Del Prete
authors: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Giovanna
authors: G
authors: Grandinetti
authors: Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors: Guan-Han
authors: GH
authors: Li
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors: Jacob D
authors: JD
authors: Estes
authors: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors: Prashant
authors: P
authors: Rao
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors: Charles M
authors: CM
authors: Trubey
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors: James
authors: J
authors: Thomas
authors: National Institute of Standards and Technology, Gaithersburg, Maryland, USA.
authors: Jeffrey
authors: J
authors: Spector
authors: National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA.
authors: Donald
authors: D
authors: Bliss
authors: Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors: Avindra
authors: A
authors: Nath
authors: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland, USA.
authors: Jeffrey D
authors: JD
authors: Lifson
authors: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA ss1@nih.gov.
authors: Sriram
authors: S
authors: Subramaniam
mesh_terms: D001253:Astrocytes / Q000648:ultrastructure / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000648:ultrastructure / Q000821:virology; D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure / Q000821:virology*; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D046529:Microscopy, Electron, Transmission; D013569:Synapses / Q000648:ultrastructure / Q000821:virology*