[ { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/zzbff-y3d67", "eprint_id": 99678, "eprint_status": "archive", "datestamp": "2023-08-19 18:23:10", "lastmod": "2023-10-18 18:39:38", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ladinsky-M-S", "name": { "family": "Ladinsky", "given": "Mark S." }, "orcid": "0000-0002-1036-3513" }, { "id": "Khamaikawin-W", "name": { "family": "Khamaikawin", "given": "Wannisa" } }, { "id": "Jung-Yujin", "name": { "family": "Jung", "given": "Yujin" } }, { "id": "Lin-Samantha", "name": { "family": "Lin", "given": "Samantha" } }, { "id": "Lam-Jennifer", "name": { "family": "Lam", "given": "Jennifer" } }, { "id": "An-Dong-Sung", "name": { "family": "An", "given": "Dong Sung" } }, { "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990" }, { "id": "Kieffer-C", "name": { "family": "Kieffer", "given": "Collin" }, "orcid": "0000-0001-9051-3819" } ] }, "title": "Mechanisms of virus dissemination in bone marrow of HIV-1-infected humanized BLT mice", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 eLife Sciences Publications Ltd. Subject to a Creative Commons Attribution license, except where otherwise noted. \n\nData availability: Source data files have been provided for graphs from Figure 1. \n\nWe thank Andres Collazo at the Caltech Biological Imaging Facility for use of confocal and light sheet microscopes and help with image capture and analysis, Carol Garland and the Caltech Kavli Nanoscience Institute for aid in maintaining the TF30 electron microscope, and the Gordon and Betty Moore and Beckman Foundations for gifts to Caltech to support electron microscopy. This research was supported by the Rosalind W. Alcott post-doctoral fellowship (Caltech) and startup funding from the University of Illinois at Urbana-Champaign School of Molecular and\nCellular Biology (C.K.), NIAID 1R01AI100652-01A1, the UCLA AIDS Institute, and the UCLA Center for AIDS Research NIH/NIAID AI028697 (D.S.A.), and the National Institute of General Medical Sciences (2 P50 GM082545-08) and California HIV/AIDS Research Program (ID15-CT-017) (P.J.B.) The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The opinions, findings, and conclusions herein are those of the authors and do not necessarily represent those of The Regents of the University of California, or any of its programs. \n\nThe authors declare no competing interests.\n\n
Published - elife-46916-v2.pdf
Supplemental Material - elife-46916-supp-v1.zip
", "abstract": "Immune progenitor cells differentiate in bone marrow (BM) and then migrate to tissues. HIV-1 infects multiple BM cell types, but virus dissemination within BM has been poorly understood. We used light microscopy and electron tomography to elucidate mechanisms of HIV-1 dissemination within BM of HIV-1\u2013infected BM/thymus/liver (BLT) mice. Tissue clearing combined with confocal and light sheet fluorescence microscopy revealed distinct populations of HIV-1 p24-producing cells in BM early after infection, and quantification of these populations identified macrophages as the principal subset of virus-producing cells in BM over time. Electron tomography demonstrated three modes of HIV-1 dissemination in BM: (i) semi-synchronous budding from T-cell and macrophage membranes, (ii) mature virus association with virus-producing T-cell uropods contacting putative target cells, and (iii) macrophages engulfing HIV-1\u2013producing T-cells and producing virus within enclosed intracellular compartments that fused to invaginations with access to the extracellular space. These results illustrate mechanisms by which the specialized environment of the BM can promote virus spread locally and to distant lymphoid tissues.", "date": "2019-10-28", "date_type": "published", "publication": "eLife", "volume": "8", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e46916", "id_number": "CaltechAUTHORS:20191105-112449359", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191105-112449359", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "Caltech" }, { "agency": "University of Illinois Urbana-Champaign" }, { "agency": "NIH", "grant_number": "1R01AI100652-01A1" }, { "agency": "UCLA" }, { "agency": "NIH", "grant_number": "AI028697" }, { "agency": "NIH", "grant_number": "2 P50 GM082545-08" }, { "agency": "California HIV/AIDS Research Program", "grant_number": "ID15-CT-017" } ] }, "local_group": { "items": [ { "id": "Kavli-Nanoscience-Institute" } ] }, "doi": "10.7554/elife.46916", "pmcid": "PMC6839903", "primary_object": { "basename": "elife-46916-supp-v1.zip", "url": "https://authors.library.caltech.edu/records/zzbff-y3d67/files/elife-46916-supp-v1.zip" }, "related_objects": [ { "basename": "elife-46916-v2.pdf", "url": "https://authors.library.caltech.edu/records/zzbff-y3d67/files/elife-46916-v2.pdf" } ], "resource_type": "article", "pub_year": "2019", "author_list": "Ladinsky, Mark S.; Khamaikawin, Wannisa; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/1g3tx-dff49", "eprint_id": 74455, "eprint_status": "archive", "datestamp": "2023-08-19 01:32:12", "lastmod": "2023-10-24 22:39:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kieffer-C", "name": { "family": "Kieffer", "given": "Collin" }, "orcid": "0000-0001-9051-3819" }, { "id": "Ladinsky-M-S", "name": { "family": "Ladinsky", "given": "Mark S." }, "orcid": "0000-0002-1036-3513" }, { "id": "Ninh-Allen", "name": { "family": "Ninh", "given": "Allen" } }, { "id": "Galimidi-Rachel-P", "name": { "family": "Galimidi", "given": "Rachel P." } }, { "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990" } ] }, "title": "Longitudinal imaging of HIV-1 spread in humanized mice with parallel 3D immunofluorescence and electron tomography", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017, Kieffer et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. \n\nReceived November 15, 2016; Accepted February 13, 2017; Published February 15, 2017. \n\nWe thank Andres Collazo and the Caltech Biological Imaging Center for use of the Zeiss LSM-710 and 880 confocal microscopes and help with image capture and analysis, Carol Garland and Alasdair McDowall for help maintaining electron microscopes, Viviana Gradinaru and Ben Deverman for advice about tissue clearing methodologies, Wesley Sundquist for a rabbit polyclonal anti-HIV-1 p24 antibody, and Michel Nussenzweig for the pNL4-3envYU2 HIV-1. This work was supported by the National Institutes of Health (2 P50 GM082545-06; WI Sundquist, PI), Ragon Institute and Rosalind W. Alcott post-doctoral fellowships (CK), gifts from the Gordon and Betty Moore Foundation and the Agouron Institute to support electron microscopy at Caltech, and funds provided by The Regents of the University of California, Research Grants Program Office, California HIV/AIDS Research Program, Grant Number ID15-CT-017. The opinions, findings, and conclusions herein are those of the author and not necessarily represent those The Regents of the University of California, or any of its programs.\n\nThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.\n\nCompeting Interests:\nThe authors declare that they have no competing interests.\n\nSupplemental Material - elife-23282-supp-v1.zip
", "abstract": "Dissemination of HIV-1 throughout lymphoid tissues leads to systemic virus spread following infection. We combined tissue clearing, 3D-immunofluorescence, and electron tomography (ET) to longitudinally assess early HIV-1 spread in lymphoid tissues in humanized mice. Immunofluorescence revealed peak infection density in gut at 10-12 days post-infection when blood viral loads were low. Human CD4+ T-cells and HIV-1-infected cells localized predominantly to crypts and the lower third of intestinal villi. Free virions and infected cells were not readily detectable by ET at 5-days post-infection, whereas HIV-1-infected cells surrounded by pools of free virions were present in ~10% of intestinal crypts by 10-12 days. ET of spleen revealed thousands of virions released by individual cells and discreet cytoplasmic densities near sites of prolific virus production. These studies highlight the importance of multiscale imaging of HIV-1-infected tissues and are adaptable to other animal models and human patient samples.", "date": "2017-02-15", "date_type": "published", "publication": "eLife", "volume": "6", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e23282", "id_number": "CaltechAUTHORS:20170222-084228926", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170222-084228926", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "2P50GM082545-06" }, { "agency": "Ragon Institute" }, { "agency": "Rosalind W. Alcott Postdoctoral Fellowship" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Agouron Institute" }, { "agency": "California HIV/AIDS Research Program", "grant_number": "ID15-CT-017" } ] }, "collection": "CaltechAUTHORS", "doi": "10.7554/eLife.23282", "pmcid": "PMC5338924", "primary_object": { "basename": "elife-23282-supp-v1.zip", "url": "https://authors.library.caltech.edu/records/1g3tx-dff49/files/elife-23282-supp-v1.zip" }, "resource_type": "article", "pub_year": "2017", "author_list": "Kieffer, Collin; Ladinsky, Mark S.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/rft4w-pac30", "eprint_id": 50219, "eprint_status": "archive", "datestamp": "2023-08-20 04:19:19", "lastmod": "2023-10-17 22:51:27", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Basham-K-J", "name": { "family": "Basham", "given": "Kaitlin J." } }, { "id": "Leonard-C-J", "name": { "family": "Leonard", "given": "Christopher J." } }, { "id": "Kieffer-C", "name": { "family": "Kieffer", "given": "Collin" }, "orcid": "0000-0001-9051-3819" }, { "id": "Shelton-D-N", "name": { "family": "Shelton", "given": "Dawne N." } }, { "id": "McDowell-M-E", "name": { "family": "McDowell", "given": "Maria E." } }, { "id": "Bhonde-V-R", "name": { "family": "Bhonde", "given": "Vasudev R." } }, { "id": "Looper-R-E", "name": { "family": "Looper", "given": "Ryan E." } }, { "id": "Welm-B-E", "name": { "family": "Welm", "given": "Bryan E." } } ] }, "title": "Dioxin Exposure Blocks Lactation Through a Direct Effect on Mammary Epithelial Cells Mediated by the Aryl Hydrocarbon Receptor Repressor", "ispublished": "pub", "full_text_status": "public", "keywords": "lactation, AHR, TCDD, AHRR, ARNT, mammary gland", "note": "\u00a9 2014 The Author. Published by Oxford University Press on behalf of the Society of Toxicology. \n\nReceived April 4, 2014. Revision received September 5, 2014. Accepted September 23, 2014. First published online: September 29, 2014. \n\nWe thank Drs James Bear (University of North Carolina, Chapel Hill, NC) and Thomas Marshall (University of Utah, Salt Lake City, UT) for providing the pLentiLox5.0-GFP vector; Dr Mark Hahn (Woods Hole Oceanographic Institution, Woods Hole, MA) for providing pcDNA-mAhRR, and Dr Oliver Hankinson (University of California, Los Angeles, CA) for providing pACTAG-HA-AHR and pACTAG-HA-ARNT. The authors declare that they have no conflicts of interest. \n\nThe National Institutes of Health [R01-CA143815, R01-CA140296, R01-GM090082]; the Department of Defense Breast Cancer Research Program [W81XWH-09-01-04310]; the National Institutes of Health Development Biology Training Grant [5T32 HD07491 to K.J.B.].\n\nAccepted Version - Basham_2014.pdf
", "abstract": "In mammals, lactation is a rich source of nutrients and antibodies for newborn animals. However, millions of mothers each year experience an inability to breastfeed. Exposure to several environmental toxicants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been strongly implicated in impaired mammary differentiation and lactation. TCDD and related polyhalogenated aromatic hydrocarbons are widespread industrial pollutants that activate the aryl hydrocarbon receptor (AHR). Despite many epidemiological and animal studies, the molecular mechanism through which AHR signaling blocks lactation remains unclear. We employed in vitro models of mammary differentiation to recapitulate lactogenesis in the presence of toxicants. We demonstrate AHR agonists directly block milk production in isolated mammary epithelial cells. Moreover, we define a novel role for the aryl hydrocarbon receptor repressor (AHRR) in mediating this response. Our mechanistic studies suggest AHRR is sufficient to block transcription of the milk gene \u03b2-casein. Since TCDD is a prevalent environmental pollutant that affects women worldwide, our results have important public health implications for newborn nutrition.", "date": "2015-01", "date_type": "published", "publication": "Toxicological Sciences", "volume": "143", "number": "1", "publisher": "Oxford University Press", "pagerange": "36-45", "id_number": "CaltechAUTHORS:20141006-154533830", "issn": "1096-6080", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20141006-154533830", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01-CA143815" }, { "agency": "NIH", "grant_number": "R01-CA140296" }, { "agency": "NIH", "grant_number": "R01-GM090082" }, { "agency": "Department of Defense", "grant_number": "W81XWH-09-01-04310" }, { "agency": "NIH", "grant_number": "5T32-HD07491" } ] }, "doi": "10.1093/toxsci/kfu203", "pmcid": "PMC4274378", "primary_object": { "basename": "Basham_2014.pdf", "url": "https://authors.library.caltech.edu/records/rft4w-pac30/files/Basham_2014.pdf" }, "resource_type": "article", "pub_year": "2015", "author_list": "Basham, Kaitlin J.; Leonard, Christopher J.; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/r9tq9-asg39", "eprint_id": 45402, "eprint_status": "archive", "datestamp": "2023-08-19 22:56:19", "lastmod": "2023-10-26 17:58:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ladinsky-M-S", "name": { "family": "Ladinsky", "given": "Mark S." }, "orcid": "0000-0002-1036-3513" }, { "id": "Kieffer-C", "name": { "family": "Kieffer", "given": "Collin" }, "orcid": "0000-0001-9051-3819" }, { "id": "Olson-G", "name": { "family": "Olson", "given": "Gregory" } }, { "id": "Deruaz-M", "name": { "family": "Deruaz", "given": "Maud" } }, { "id": "Vrbanac-V", "name": { "family": "Vrbanac", "given": "Vladimir" } }, { "id": "Tager-A-M", "name": { "family": "Tager", "given": "Andrew M." } }, { "id": "Kwon-Douglas-S", "name": { "family": "Kwon", "given": "Douglas S." } }, { "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990" } ] }, "title": "Electron Tomography of HIV-1 Infection in Gut-Associated Lymphoid Tissue", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2014 Ladinsky et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.\n\nReceived August 11, 2013; Accepted December 9, 2013; Published January 30, 2014.\n\nWe thank Wes Sundquist for providing anti-ESCRT and other antibodies; Yunji Wu and the Caltech Protein Expression Center for purified 2G12; Drs. Grant Jensen and Julia Greer for use of the Tecnai T12 and F30 electron microscopes, respectively, and Dr. Alasdair McDowall and Carol Garland for help maintaining the microscopes. We thank Ariane Briegel, Wes Sundquist, Bruce Walker, Cora Woodward and Mark Yeager for helpful discussions, and Bruce Walker, Grant Jensen and Cora Woodward for critical reading of the manuscript.\n\nFunding:\n\nThis work was supported by the National Institutes of Health (2 P50 GM082545-06; WI Sundquist, PI), a Ragon Institute post-doctoral fellowship (CK), and gifts from the Gordon and Betty Moore Foundation and the Agouron Institute to support electron microscopy at Caltech. DSK is supported by an NIH K08 Award (K08 AI084546-04) and a fellowship from the Burroughs Wellcome Fund. The MGH Humanized Mouse Program is supported by the Harvard University Center for AIDS Research (P30 AI060354). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.\n\n\nAuthor Contributions:\n\nConceived and designed the experiments: MSL DSK PJB. Performed the\nexperiments: MSL GO. Analyzed the data: MSL CK GO DSK PJB.\nContributed reagents/materials/analysis tools: GO MD VV AMT DSK.\nWrote the paper: MSL CK DSK PJB.\n\nPublished - journal.ppat.1003899.pdf
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Supplemental Material - journal.ppat.1003899.s008.tif
Supplemental Material - journal.ppat.1003899.s009.mov
Supplemental Material - journal.ppat.1003899.s010.mov
Supplemental Material - journal.ppat.1003899.s011.mov
Supplemental Material - journal.ppat.1003899.s012.mov
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Supplemental Material - journal.ppat.1003899.s014.docx
", "abstract": "Critical aspects of HIV-1 infection occur in mucosal tissues, particularly in the gut, which contains large numbers of HIV-1 target cells that are depleted early in infection. We used electron tomography (ET) to image HIV-1 in gut-associated lymphoid tissue (GALT) of HIV-1\u2013infected humanized mice, the first three-dimensional ultrastructural examination of HIV-1 infection in vivo. Human immune cells were successfully engrafted in the mice, and following infection with HIV-1, human T cells were reduced in GALT. Virions were found by ET at all stages of egress, including budding immature virions and free mature and immature viruses. Immuno-electron microscopy verified the virions were HIV-1 and showed CD4 sequestration in the endoplasmic reticulum of infected cells. Observation of HIV-1 in infected GALT tissue revealed that most HIV-1\u2013infected cells, identified by immunolabeling and/or the presence of budding virions, were localized to intestinal crypts with pools of free virions concentrated in spaces between cells. Fewer infected cells were found in mucosal regions and the lamina propria. The preservation quality of reconstructed tissue volumes allowed details of budding virions, including structures interpreted as host-encoded scission machinery, to be resolved. Although HIV-1 virions released from infected cultured cells have been described as exclusively mature, we found pools of both immature and mature free virions within infected tissue. The pools could be classified as containing either mostly mature or mostly immature particles, and analyses of their proximities to the cell of origin supported a model of semi-synchronous waves of virion release. In addition to HIV-1 transmission by pools of free virus, we found evidence of transmission via virological synapses. Three-dimensional EM imaging of an active infection within tissue revealed important differences between cultured cell and tissue infection models and furthered the ultrastructural understanding of HIV-1 transmission within lymphoid tissue.", "date": "2014-01", "date_type": "published", "publication": "PLoS Pathogens", "volume": "10", "number": "1", "publisher": "Public Library of Science", "pagerange": "Art. No. e1003899", "id_number": "CaltechAUTHORS:20140501-094612824", "issn": "1553-7366", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20140501-094612824", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "2 P50 GM082545-06" }, { "agency": "Ragon Institute" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Agouron Institute" }, { "agency": "NIH", "grant_number": "K08 AI084546-04" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "Harvard University Center for AIDS Research", "grant_number": "P30 AI060354" } ] }, "doi": "10.1371/journal.ppat.1003899", "pmcid": "PMC3907528", "primary_object": { "basename": "journal.ppat.1003899.s012.mov", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s012.mov" }, "related_objects": [ { "basename": "journal.ppat.1003899.s013.mov", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s013.mov" }, { "basename": "journal.ppat.1003899.s014.docx", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s014.docx" }, { "basename": "journal.ppat.1003899.s008.tif", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s008.tif" }, { "basename": "journal.ppat.1003899.s009.mov", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s009.mov" }, { "basename": "journal.ppat.1003899.s004.tif", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s004.tif" }, { "basename": "journal.ppat.1003899.s006.tif", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s006.tif" }, { "basename": "journal.ppat.1003899.s007.tif", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s007.tif" }, { "basename": "journal.ppat.1003899.s001.tif", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s001.tif" }, { "basename": "journal.ppat.1003899.s003.tif", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s003.tif" }, { "basename": "journal.ppat.1003899.s005.tif", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s005.tif" }, { "basename": "journal.ppat.1003899.s010.mov", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s010.mov" }, { "basename": "journal.ppat.1003899.s011.mov", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s011.mov" }, { "basename": "journal.ppat.1003899.pdf", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.pdf" }, { "basename": "journal.ppat.1003899.s002.tif", "url": "https://authors.library.caltech.edu/records/r9tq9-asg39/files/journal.ppat.1003899.s002.tif" } ], "resource_type": "article", "pub_year": "2014", "author_list": "Ladinsky, Mark S.; Kieffer, Collin; et el." }, { "id": "https://authors.library.caltech.eduhttps://authors.library.caltech.edu/records/0qvff-k2k46", "eprint_id": 24664, "eprint_status": "archive", "datestamp": "2023-08-19 20:03:10", "lastmod": "2023-10-23 23:33:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wright-E-R", "name": { "family": "Wright", "given": "Elizabeth R." } }, { "id": "Schooler-J-B", "name": { "family": "Schooler", "given": "Jordan B." } }, { "id": "Ding-H-Jane", "name": { "family": "Ding", "given": "H. Jane" } }, { "id": "Kieffer-C", "name": { "family": "Kieffer", "given": "Collin" }, "orcid": "0000-0001-9051-3819" }, { "id": "Fillmore-C", "name": { "family": "Fillmore", "given": "Christopher" } }, { "id": "Sundquist-W-I", "name": { "family": "Sundquist", "given": "Wesley I." } }, { "id": "Jensen-G-J", "name": { "family": "Jensen", "given": "Grant J." }, "orcid": "0000-0003-1556-4864" } ] }, "title": "Electron cryotomography of immature HIV-1 virions reveals the structure of the CA and SP1 Gag shells", "ispublished": "pub", "full_text_status": "public", "keywords": "electron cryotomography, Gag, human immunodeficiency virus type 1 (HIV-1), spacer peptide 1 (SP1)", "note": "\u00a9 2007 European Molecular Biology Organization. \n\nReceived: 3 January 2007; accepted: 5 March 2007; published online: 29 March 2007. \n\nThis work was supported in part by NIH Grant PO1 GM66521 (to WIS and GJJ), NIH Grant A145405 (to WIS), NIH Grant F32 GM075543 (to ERW), the Beckman Institute at Caltech, and gifts to Caltech from the Ralph M Parsons Foundation, the Agouron Institute, and the Gordon and Betty Moore Foundation. \n\nSupplementary data are available at The EMBO Journal Online (http://www.embojournal.org).\n\nSupplemental Material - WRIemboj07.mov
", "abstract": "The major structural elements of retroviruses are contained in a single polyprotein, Gag, which in human immunodeficiency virus type 1 (HIV-1) comprises the MA, CA, spacer peptide 1 (SP1), NC, SP2, and p6 polypeptides. In the immature HIV-1 virion, the domains of Gag are arranged radially with the N-terminal MA domain at the membrane and C-terminal NC-SP2-p6 region nearest to the center. Here, we report the three-dimensional structures of individual immature HIV-1 virions, as obtained by electron cryotomography. The concentric shells of the Gag polyprotein are clearly visible, and radial projections of the different Gag layers reveal patches of hexagonal order within the CA and SP1 shells. Averaging well-ordered unit cells leads to a model in which each CA hexamer is stabilized by a bundle of six SP1 helices. This model suggests why the SP1 spacer is essential for assembly of the Gag lattice and how cleavage between SP1 and CA acts as a structural switch controlling maturation.", "date": "2007-04-18", "date_type": "published", "publication": "EMBO Journal", "volume": "26", "number": "8", "publisher": "European Molecular Biology Organization", "pagerange": "2218-2226", "id_number": "CaltechAUTHORS:20110803-142323319", "issn": "0261-4189", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20110803-142323319", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "PO1 GM66521" }, { "agency": "NIH", "grant_number": "A145405" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32 GM075543" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Ralph M. Parsons Foundation" }, { "agency": "Agouron Institute" }, { "agency": "Gordon and Betty Moore Foundation" } ] }, "doi": "10.1038/sj.emboj.7601664", "pmcid": "PMC1852790", "primary_object": { "basename": "WRIemboj07.mov", "url": "https://authors.library.caltech.edu/records/0qvff-k2k46/files/WRIemboj07.mov" }, "resource_type": "article", "pub_year": "2007", "author_list": "Wright, Elizabeth R.; Schooler, Jordan B.; et el." } ]