{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T07:12:10Z","timestamp":1779001930713,"version":"3.51.4"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,4,8]],"date-time":"2014-04-08T00:00:00Z","timestamp":1396915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Ricin is a member of the ubiquitous family of plant and bacterial AB toxins that gain entry into the cytosol of host cells through receptor-mediated endocytosis and retrograde traffic through the<jats:italic>trans<\/jats:italic>-Golgi network (TGN) and endoplasmic reticulum (ER). While a few ricin toxin-specific neutralizing monoclonal antibodies (MAbs) have been identified, the mechanisms by which these antibodies prevent toxin-induced cell death are largely unknown. Using immunofluorescence confocal microscopy and a TGN-specific sulfation assay, we demonstrate that 24B11, a MAb against ricin\u2019s binding subunit (RTB), associates with ricin in solution or when prebound to cell surfaces and then markedly enhances toxin uptake into host cells. Following endocytosis, however, toxin-antibody complexes failed to reach the TGN; instead, they were shunted to Rab7-positive late endosomes and LAMP-1-positive lysosomes. Monovalent 24B11 Fab fragments also interfered with toxin retrograde transport, indicating that neither cross-linking of membrane glycoproteins\/glycolipids nor the recently identified intracellular Fc receptor is required to derail ricin en route to the TGN. Identification of the mechanism(s) by which antibodies like 24B11 neutralize ricin will advance our fundamental understanding of protein trafficking in mammalian cells and may lead to the discovery of new classes of toxin inhibitors and therapeutics for biodefense and emerging infectious diseases.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Ricin is the prototypic member of the AB family of medically important plant and bacterial toxins that includes cholera and Shiga toxins. Ricin is also a category B biothreat agent. Despite ongoing efforts to develop vaccines and antibody-based therapeutics against ricin, very little is known about the mechanisms by which antibodies neutralize this toxin. In general, it is thought that antibodies simply prevent toxins from attaching to cell surface receptors or promote their clearance through Fc receptor (FcR)-mediated uptake. In this report, however, we describe a neutralizing monoclonal antibody (MAb) against ricin\u2019s binding subunit (RTB) that not only associates with ricin after the toxin has bound to the cell\u2019s surface but actually enhances toxin uptake into host cells. Following endocytosis, the antibody-toxin complexes are then routed for degradation. The results of this study are important because they reveal a previously unappreciated role for B-subunit-specific antibodies in intracellular neutralization of ricin toxin.<\/jats:p>","DOI":"10.1128\/mbio.00995-13","type":"journal-article","created":{"date-parts":[[2014,4,9]],"date-time":"2014-04-09T06:36:14Z","timestamp":1397025374000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Antibody-Mediated Inhibition of Ricin Toxin Retrograde Transport"],"prefix":"10.1128","volume":"5","author":[{"given":"Anastasiya","family":"Yermakova","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA"},{"name":"Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tove Irene","family":"Klokk","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Centre for Cancer Biomedicine, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York, USA"},{"name":"Division of Translational Medicine, Wadsworth Center, New York State Department of Health, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten","family":"Sandvig","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Centre for Cancer Biomedicine, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway"},{"name":"Department of Biosciences, University of Oslo, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Mantis","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA"},{"name":"Department of Biomedical Sciences, School of Public Health, University at Albany, Albany, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2279"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/82_2011_193"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/326624a0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)33344-6"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-013-1111-z"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.12.009"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.2.253"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20040742"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/82_2011_181"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/149737"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.24063"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00543-12"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.4.926-941.2004"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.4049\/jimmunol.138.10.3339","article-title":"Identification and characterization of a monoclonal antibody recognizing a galactose-binding domain of the toxin ricin","volume":"138","author":"Colombatti M","year":"1987","unstructured":"ColombattiM JohnsonVG SkopickiHA FendleyB LewisMS YouleRJ . 1987. 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