{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:42:33Z","timestamp":1792806153223,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The American Heart Association (AHA)","award":["0855421E"],"award-info":[{"award-number":["0855421E"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The American Heart Association (AHA)","award":["12GRNT120\/0313"],"award-info":[{"award-number":["12GRNT120\/0313"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The American Heart Association (AHA)","award":["17GRNT33460327"],"award-info":[{"award-number":["17GRNT33460327"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The Enduring Hearts Foundation","award":["0855421E"],"award-info":[{"award-number":["0855421E"]}]},{"name":"The Enduring Hearts Foundation","award":["12GRNT120\/0313"],"award-info":[{"award-number":["12GRNT120\/0313"]}]},{"name":"The Enduring Hearts Foundation","award":["17GRNT33460327"],"award-info":[{"award-number":["17GRNT33460327"]}]},{"name":"Biodesign Institute, Arizona State University","award":["0855421E"],"award-info":[{"award-number":["0855421E"]}],"id":[{"id":"https:\/\/ror.org\/03efmqc40","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Biodesign Institute, Arizona State University","award":["12GRNT120\/0313"],"award-info":[{"award-number":["12GRNT120\/0313"]}],"id":[{"id":"https:\/\/ror.org\/03efmqc40","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Biodesign Institute, Arizona State University","award":["17GRNT33460327"],"award-info":[{"award-number":["17GRNT33460327"]}],"id":[{"id":"https:\/\/ror.org\/03efmqc40","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Immune cell invasion after the transplantation of solid organs is directed by chemokines binding to glycosaminoglycans (GAGs), creating gradients that guide immune cell infiltration. Renal transplant is the preferred treatment for end stage renal failure, but organ supply is limited and allografts are often injured during transport, surgery or by cytokine storm in deceased donors. While treatment for adaptive immune responses during rejection is excellent, treatment for early inflammatory damage is less effective. Viruses have developed highly active chemokine inhibitors as a means to evade host responses. The myxoma virus-derived M-T7 protein blocks chemokine: GAG binding. We have investigated M-T7 and also antisense (ASO) as pre-treatments to modify chemokine: GAG interactions to reduce donor organ damage. Immediate pre-treatment of donor kidneys with M-T7 to block chemokine: GAG binding significantly reduced the inflammation and scarring in subcapsular and subcutaneous allografts. Antisense to N-deacetylase N-sulfotransferase1 (ASONdst1) that modifies heparan sulfate, was less effective with immediate pre-treatment, but reduced scarring and C4d staining with donor pre-treatment for 7 days before transplantation. Grafts with conditional Ndst1 deficiency had reduced inflammation. Local inhibition of chemokine: GAG binding in donor organs immediately prior to transplant provides a new approach to reduce transplant damage and graft loss.<\/jats:p>","DOI":"10.3390\/pathogens11050588","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T21:36:06Z","timestamp":1652736966000},"page":"588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Virus-Derived Chemokine Modulating Protein Pre-Treatment Blocks Chemokine\u2013Glycosaminoglycan Interactions and Significantly Reduces Transplant Immune Damage"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3441-5955","authenticated-orcid":false,"given":"Isabela R.","family":"Zanetti","sequence":"first","affiliation":[{"name":"Center for Personalized Diagnostics (CPD), Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8596-9683","authenticated-orcid":false,"given":"Michelle","family":"Burgin","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics (CPD), Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8808-8996","authenticated-orcid":false,"given":"Liqiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics (CPD), Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve T.","family":"Yeh","sequence":"additional","affiliation":[{"name":"Ionis Pharmaceuticals, Inc., Carlsbad, CA 92008, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sriram","family":"Ambadapadi","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics (CPD), Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Kilbourne","sequence":"additional","affiliation":[{"name":"Department of Animal Care and Technologies, Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4133-474X","authenticated-orcid":false,"given":"Jordan R.","family":"Yaron","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics (CPD), Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"},{"name":"School for Engineering of Matter, Transport and Energy, Ira A. Fulton Schools of Engineering, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Animal Care and Technologies, Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Daggett-Vondras","sequence":"additional","affiliation":[{"name":"Department of Animal Care and Technologies, Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fonseca","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics (CPD), Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Boyd","sequence":"additional","affiliation":[{"name":"Center for Applied Structural Discovery, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dara","family":"Wakefield","sequence":"additional","affiliation":[{"name":"Pathology Department, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Clapp","sequence":"additional","affiliation":[{"name":"Pathology Department, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3397-9310","authenticated-orcid":false,"given":"Efrem","family":"Lim","sequence":"additional","affiliation":[{"name":"The Biodesign Center of Fundamental and Applied Microbiomics, Center for Evolution and Medicine, School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"The Department of Tumor Surgery, Second Hospital of Lanzhou University, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Lucas","sequence":"additional","affiliation":[{"name":"Center for Personalized Diagnostics (CPD), Biodesign Institute, Arizona State University (ASU), Tempe, AZ 85287, USA"},{"name":"Center for Immunotherapy, Vaccines and Virotherapy (CIVV), Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1001\/jama.2017.4046","article-title":"Assessment of Global Kidney Health Care Status","volume":"317","author":"Bello","year":"2017","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2165\/00003495-200868001-00002","article-title":"Trends in Kidney Transplantation over the Past Decade","volume":"68","author":"Knoll","year":"2008","journal-title":"Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1046\/j.1523-1755.2003.00272.x","article-title":"Relationship between duration of brain death and hemodynamic (in) stability on progressive dysfunction and increased immunologic activation of donor kidneys","volume":"64","author":"Molema","year":"2003","journal-title":"Kidney Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1097\/00007890-199806270-00001","article-title":"Effects of explosive brain death on cytokine activation of peripheral organs in the rat","volume":"65","author":"Takada","year":"1998","journal-title":"Transplantation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/imm.12332","article-title":"Transplantation and inflammation: Implications for the modification of chemokine function","volume":"143","author":"Barker","year":"2014","journal-title":"Immunology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1053\/ajkd.2001.22076","article-title":"Expression of Chemokines and Chemokine Receptors During Human Renal Transplant Rejection","volume":"37","author":"Segerer","year":"2001","journal-title":"Am. 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