{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T14:47:20Z","timestamp":1793026040594,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 AG032958"],"award-info":[{"award-number":["P01 AG032958"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL152961"],"award-info":[{"award-number":["P01 HL152961"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R33HL141794"],"award-info":[{"award-number":["R33HL141794"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21HL152350"],"award-info":[{"award-number":["R21HL152350"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL151984"],"award-info":[{"award-number":["R01HL151984"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA046934"],"award-info":[{"award-number":["P30 CA046934"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Colorado Comprehensive Cancer Center","id":[{"id":"https:\/\/ror.org\/04cqn7d42","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Herpes zoster (HZ; shingles) caused by varicella zoster virus reactivation increases stroke risk for up to 1 year after HZ. The underlying mechanisms are unclear, however, the development of stroke distant from the site of zoster (eg, thoracic, lumbar, sacral) that can occur months after resolution of rash points to a long-lasting, virus-induced soluble factor (or factors) that can trigger thrombosis and\/or vasculitis. Herein, we investigated the content and contributions of circulating plasma exosomes from HZ and non-HZ patient samples. Compared with non-HZ exosomes, HZ exosomes (1) contained proteins conferring a prothrombotic state to recipient cells and (2) activated platelets leading to the formation of platelet-leukocyte aggregates. Exosomes 3 months after HZ yielded similar results and also triggered cerebrovascular cells to secrete the proinflammatory cytokines, interleukin 6 and 8. These results can potentially change clinical practice through addition of antiplatelet agents for HZ and initiatives to increase HZ vaccine uptake to decrease stroke risk.<\/jats:p>","DOI":"10.1093\/infdis\/jiac405","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T16:54:11Z","timestamp":1664902451000},"page":"993-1001","source":"Crossref","is-referenced-by-count":24,"title":["Zoster-Associated Prothrombotic Plasma Exosomes and Increased Stroke Risk"],"prefix":"10.1093","volume":"227","author":[{"given":"Andrew N","family":"Bubak","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Coughlan","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle","family":"Posey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J","family":"Saviola","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy S","family":"Niemeyer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena W R","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Bustos","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Solano","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen K","family":"Tyring","sequence":"additional","affiliation":[{"name":"Center for Clinical Studies and Department of Dermatology, McGovern School of Medicine, University of Texas Health Science Center , Houston, Texas , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassidy","family":"Delaney","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith B","family":"Neeves","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"},{"name":"Department of Bioengineering, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Mahalingam","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk C","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0549-812X","authenticated-orcid":false,"given":"Maria A","family":"Nagel","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"},{"name":"Department of Ophthalmology, University of Colorado Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"2023070503462875900_jiac405-B1","doi-asserted-by":"crossref","first-page":"S314","DOI":"10.1093\/infdis\/174.Supplement_3.S314","article-title":"Varicella-zoster virus epidemiology\u2014a changing scene?","volume":"174","author":"Fairley","year":"1996","journal-title":"J Infect Dis"},{"key":"2023070503462875900_jiac405-B2","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1177\/003335491012500613","article-title":"Varicella seroprevalence in the U.S.: data from the National Health and Nutrition Examination Survey, 1999\u20132004","volume":"125","author":"Reynolds","year":"2010","journal-title":"Public Health Rep"},{"key":"2023070503462875900_jiac405-B3","first-page":"1","article-title":"Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP)","volume":"57","author":"Harpaz","year":"2008","journal-title":"MMWR Recomm Rep"},{"key":"2023070503462875900_jiac405-B4","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s12879-017-2278-z","article-title":"A meta-analysis of stroke risk following herpes zoster infection","volume":"17","author":"Marra","year":"2017","journal-title":"BMC Infect Dis"},{"key":"2023070503462875900_jiac405-B5","doi-asserted-by":"crossref","first-page":"S107","DOI":"10.1093\/infdis\/jiy425","article-title":"Varicella zoster virus vasculopathy","volume":"218","author":"Nagel","year":"2018","journal-title":"J Infect Dis"},{"key":"2023070503462875900_jiac405-B6","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1097\/PEC.0b013e3181fe91cd","article-title":"Chickenpox is not always benign: postvaricella purpura fulminans requires prompt and aggressive treatment","volume":"26","author":"Fluri","year":"2010","journal-title":"Pediatr Emerg Care"},{"key":"2023070503462875900_jiac405-B7","first-page":"529","article-title":"Postvaricella purpura fulminans with no evidence of disseminated intravascular coagulation (DIC) or protein S deficiency","volume":"108","author":"Sharma","year":"2010","journal-title":"J Indian Med Assoc"},{"key":"2023070503462875900_jiac405-B8","doi-asserted-by":"crossref","first-page":"917.e1","DOI":"10.1016\/j.jstrokecerebrovasdis.2012.04.013","article-title":"Cerebral venous sinus thrombosis: association with primary varicella zoster virus infection","volume":"21","author":"Siddiqi","year":"2012","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"2023070503462875900_jiac405-B9","first-page":"72","article-title":"Deep vein thrombosis: a rare signature of herpes zoster","volume":"62","author":"Maity","year":"2014","journal-title":"J Assoc Physicians India"},{"key":"2023070503462875900_jiac405-B10","first-page":"001171","article-title":"Cerebral venous thrombosis and acute pulmonary embolism following varicella infection","volume":"6","author":"Khan","year":"2019","journal-title":"Eur J Case Rep Intern Med"},{"key":"2023070503462875900_jiac405-B11","doi-asserted-by":"crossref","first-page":"219","DOI":"10.4103\/0028-3886.279658","article-title":"Acute herpes zoster followed by cerebral venous sinus thrombosis","volume":"68","author":"Zhu","year":"2020","journal-title":"Neurol India"},{"key":"2023070503462875900_jiac405-B12","first-page":"103165","article-title":"Cerebral venous sinus thrombosis as a complication of primary varicella infection in a child, case report","volume":"73","author":"Badour","year":"2021","journal-title":"Ann Med Surg (Lond)"},{"key":"2023070503462875900_jiac405-B13","doi-asserted-by":"crossref","first-page":"e927699","DOI":"10.12659\/AJCR.927699","article-title":"Chronic headache and cerebral venous sinus thrombosis due to varicella zoster virus infection: a case report and review of the literature","volume":"22","author":"Alamlih","year":"2021","journal-title":"Am J Case Rep"},{"key":"2023070503462875900_jiac405-B14","doi-asserted-by":"crossref","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"2023070503462875900_jiac405-B15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.thromres.2017.09.019","article-title":"Breast-cancer extracellular vesicles induce platelet activation and aggregation by tissue factor-independent and -dependent mechanisms","volume":"159","author":"Gomes","year":"2017","journal-title":"Thromb Res"},{"key":"2023070503462875900_jiac405-B16","doi-asserted-by":"crossref","first-page":"716","DOI":"10.3390\/cells8070716","article-title":"Novel aspects of extracellular vesicles as mediators of cancer-associated thrombosis","volume":"8","author":"Almeida","year":"2019","journal-title":"Cells"},{"key":"2023070503462875900_jiac405-B17","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1007\/s13365-020-00830-7","article-title":"Acute zoster plasma contains elevated amyloid, correlating with A\u03b242 and amylin levels, and is amyloidogenic","volume":"26","author":"Bubak","year":"2020","journal-title":"J Neurovirol"},{"key":"2023070503462875900_jiac405-B18","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nmeth.4256","article-title":"Msfragger: ultrafast and comprehensive peptide identification in mass spectrometry\u2013based proteomics","volume":"14","author":"Kong","year":"2017","journal-title":"Nat Methods"},{"key":"2023070503462875900_jiac405-B19","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1172\/JCI6042","article-title":"Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin","volume":"103","author":"Kahn","year":"1999","journal-title":"J Clin Invest"},{"key":"2023070503462875900_jiac405-B20","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1111\/jth.15668","article-title":"Activation mechanism dependent surface exposure of cellular factor XIII on activated platelets and platelet microparticles","volume":"20","author":"Somodi","year":"2022","journal-title":"J Thromb Haemost"},{"key":"2023070503462875900_jiac405-B21","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1182\/blood.V95.5.1694.005k24_1694_1702","article-title":"Surface expression and functional characterization of \u03b1-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin","volume":"95","author":"Alberio","year":"2000","journal-title":"Blood"},{"key":"2023070503462875900_jiac405-B22","doi-asserted-by":"crossref","first-page":"e1103","DOI":"10.1212\/NXI.0000000000001103","article-title":"Targeted RNA sequencing of VZV-infected brain vascular adventitial fibroblasts indicates that amyloid may be involved in VZV vasculopathy","volume":"9","author":"Bubak","year":"2021","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2023070503462875900_jiac405-B23","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1161\/CIRCULATIONAHA.111.078915","article-title":"Transthyretin (TTR) cardiac amyloidosis","volume":"126","author":"Ruberg","year":"2012","journal-title":"Circulation"},{"key":"2023070503462875900_jiac405-B24","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1212\/01.wnl.0000304747.38502.e8","article-title":"The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features","volume":"70","author":"Nagel","year":"2008","journal-title":"Neurology"},{"key":"2023070503462875900_jiac405-B25","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1182\/blood.2020007252","article-title":"Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19","volume":"136","author":"Hottz","year":"2020","journal-title":"Blood"},{"key":"2023070503462875900_jiac405-B26","doi-asserted-by":"crossref","first-page":"e246","DOI":"10.1212\/NXI.0000000000000246","article-title":"Proinflammatory cytokines and matrix metalloproteinases in CSF of patients with VZV vasculopathy","volume":"3","author":"Jones","year":"2016","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2023070503462875900_jiac405-B27","doi-asserted-by":"crossref","first-page":"e382","DOI":"10.1212\/NXI.0000000000000382","article-title":"Varicella zoster virus-infected cerebrovascular cells produce a proinflammatory environment","volume":"4","author":"Jones","year":"2017","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2023070503462875900_jiac405-B28","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1093\/infdis\/jir425","article-title":"Persistence of varicella zoster virus DNA in saliva after herpes zoster","volume":"204","author":"Nagel","year":"2011","journal-title":"J Infect Dis"},{"key":"2023070503462875900_jiac405-B29","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/BF00684037","article-title":"Persistence of varicella-zoster virus DNA in blood mononuclear cells of patients with varicella or zoster","volume":"2","author":"Gilden","year":"1989","journal-title":"Virus Genes"},{"key":"2023070503462875900_jiac405-B30","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1080\/13550280390201722","article-title":"Chronic varicella-zoster virus ganglionitis\u2014a possible cause of postherpetic neuralgia","volume":"9","author":"Gilden","year":"2003","journal-title":"J Neurovirol"},{"key":"2023070503462875900_jiac405-B31","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3109\/13550289509111018","article-title":"Persistence of varicella-zoster virus DNA in elderly patients with postherpetic neuralgia","volume":"1","author":"Mahalingam","year":"1995","journal-title":"J Neurovirol"},{"key":"2023070503462875900_jiac405-B32","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1212\/01.wnl.0000438228.48470.86","article-title":"Varicella-zoster virus trigeminal ganglioneuritis without rash","volume":"82","author":"Birlea","year":"2014","journal-title":"Neurology"},{"key":"2023070503462875900_jiac405-B33","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1161\/STROKEAHA.120.032788","article-title":"Herpes zoster vaccine live and risk of stroke among Medicare beneficiaries: a population-based cohort study","volume":"52","author":"Yang","year":"2021","journal-title":"Stroke"},{"key":"2023070503462875900_jiac405-B34","first-page":"e1693","article-title":"A unique case of acute cerebral venous sinus thrombosis secondary to primary varicella zoster virus infection","volume":"9","author":"Imam","year":"2017","journal-title":"Cureus"},{"key":"2023070503462875900_jiac405-B35","doi-asserted-by":"crossref","first-page":"e217498","DOI":"10.1001\/jamanetworkopen.2021.7498","article-title":"Acute ischemic stroke during the convalescent phase of asymptomatic COVID-2019 infection in men","volume":"4","author":"Tu","year":"2021","journal-title":"JAMA Netw Open"},{"key":"2023070503462875900_jiac405-B36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.hest.2021.12.002","article-title":"Severe stroke in patients admitted to intensive care unit after COVID-19 infection: pictorial essay of a case series","volume":"3","author":"Cristian","year":"2022","journal-title":"Brain Hemorrhages"},{"key":"2023070503462875900_jiac405-B37","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofac118","article-title":"Increased risk of herpes zoster in adults \u226550 years old diagnosed with COVID-19 in the United States","volume":"9","author":"Bhavsar","year":"2022","journal-title":"Open Forum Infect Dis"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiac405\/46658601\/jiac405.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/227\/8\/993\/50800269\/jiac405.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/227\/8\/993\/50800269\/jiac405.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:29Z","timestamp":1688515229000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/227\/8\/993\/6749009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,6]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,10,6]]},"published-print":{"date-parts":[[2023,4,18]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiac405","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,4,15]]},"published":{"date-parts":[[2022,10,6]]}}}