{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:58:13Z","timestamp":1791655093171,"version":"4.3.4"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","award":["321809"],"award-info":[{"award-number":["321809"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9lius Foundation","doi-asserted-by":"publisher","award":["MS568"],"award-info":[{"award-number":["MS568"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004155","name":"magnus ehrnrooth foundation","doi-asserted-by":"publisher","award":["to A.V."],"award-info":[{"award-number":["to A.V."]}],"id":[{"id":"10.13039\/501100004155","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital","award":["9X033 and 9V040"],"award-info":[{"award-number":["9X033 and 9V040"]}]},{"DOI":"10.13039\/501100006706","name":"Tampere Tuberculosis Foundation","doi-asserted-by":"publisher","award":["MS759"],"award-info":[{"award-number":["MS759"]}],"id":[{"id":"10.13039\/501100006706","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Old\u2013world orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS), characterized by acute kidney injury (AKI) with transient proteinuria. It seems plausible that proteinuria during acute HFRS is mediated by the disruption of the glomerular filtration barrier (GFB) due to vascular leakage, a hallmark of orthohantavirus\u2013caused diseases. However, direct infection of endothelial cells by orthohantaviruses does not result in increased endothelial permeability, and alternative explanations for vascular leakage and diminished GFB function are necessary. Vascular integrity is partly dependent on an intact endothelial glycocalyx, which is susceptible to cleavage by heparanase (HPSE). To understand the role of glycocalyx degradation in HFRS\u2013associated proteinuria, we investigated the levels of HPSE in urine and plasma during acute, convalescent and recovery stages of HFRS caused by Puumala orthohantavirus. HPSE levels in urine during acute HFRS were significantly increased and strongly associated with the severity of AKI and other markers of disease severity. Furthermore, increased expression of HPSE was detected in vitro in orthohantavirus\u2013infected podocytes, which line the outer surfaces of glomerular capillaries. Taken together, these findings suggest the local activation of HPSE in the kidneys of orthohantavirus\u2013infected patients with the potential to disrupt the endothelial glycocalyx, leading to increased protein leakage through the GFB, resulting in high amounts of proteinuria.<\/jats:p>","DOI":"10.3390\/v14030450","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T22:35:00Z","timestamp":1645569300000},"page":"450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Increased Heparanase Levels in Urine during Acute Puumala Orthohantavirus Infection Are Associated with Disease Severity"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9437-1010","authenticated-orcid":false,"given":"Luz E.","family":"Cabrera","sequence":"first","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Schmotz","sequence":"additional","affiliation":[{"name":"Research Program for Clinical and Molecular Metabolism, University of Helsinki, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moin A.","family":"Saleem","sequence":"additional","affiliation":[{"name":"Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol BS1 3NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4189-2415","authenticated-orcid":false,"given":"Sanna","family":"Lehtonen","sequence":"additional","affiliation":[{"name":"Research Program for Clinical and Molecular Metabolism, University of Helsinki, 00290 Helsinki, Finland"},{"name":"Department of Pathology, University of Helsinki, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2270-6824","authenticated-orcid":false,"given":"Olli","family":"Vapalahti","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, Finland"},{"name":"Virology and Immunology, Diagnostic Center, Helsinki University Hospital (HUSLAB), 00290 Helsinki, Finland"},{"name":"Department of Veterinary Biosciences, University of Helsinki, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-2345","authenticated-orcid":false,"given":"Antti","family":"Vaheri","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satu","family":"M\u00e4kel\u00e4","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Tampere University Hospital, El\u00e4m\u00e4naukio 2, 33520 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukka","family":"Mustonen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Tampere University Hospital, El\u00e4m\u00e4naukio 2, 33520 Tampere, Finland"},{"name":"Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-7479","authenticated-orcid":false,"given":"Tomas","family":"Strandin","sequence":"additional","affiliation":[{"name":"Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1128\/CMR.00062-09","article-title":"A global perspective on hantavirus ecology, epidemiology, and disease","volume":"23","author":"Jonsson","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nrmicro3066","article-title":"Uncovering the mysteries of hantavirus infections","volume":"11","author":"Vaheri","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","first-page":"727","article-title":"The fundamental role of endothelial cells in hantavirus pathogenesis","volume":"22","author":"Hepojoki","year":"2014","journal-title":"Front Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/23744235.2016.1274421","article-title":"Kidney disease in Puumala hantavirus infection","volume":"49","author":"Mustonen","year":"2017","journal-title":"Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1093\/ndt\/17.2.246","article-title":"Increased glomerular permeability in patients with nephropathia epidemica caused by Puumala hantavirus","volume":"17","author":"Koskinen","year":"2002","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mantula, P., Tiet\u00e4v\u00e4inen, J., Clement, J., Niemel\u00e4, O., P\u00f6rsti, I., Vaheri, A., Mustonen, J., M\u00e4kel\u00e4, S., and Outinen, T. (2020). Flash\u2013Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection. Pathogens, 9.","DOI":"10.3390\/pathogens9080615"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000459634","article-title":"Glomerular Proteinuria Predicts the Severity of Acute Kidney Injury in Puumala Hantavirus\u2013Induced Tubulointerstitial Nephritis","volume":"136","author":"Mantula","year":"2017","journal-title":"Nephron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1053\/j.ajkd.2014.04.030","article-title":"Hantavirus infection with severe proteinuria and podocyte foot\u2013process effacement","volume":"64","author":"Boehlke","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1159\/000433563","article-title":"Community Acquired Severe Acute Kidney Injury Caused by Hantavirus\u2013Induced Hemorrhagic Fever with Renal Syndrome Has a Favorable Outcome","volume":"130","author":"Outinen","year":"2015","journal-title":"Nephron"},{"key":"ref_10","unstructured":"Breshears, M.A., Anthony, W., and Confer, A. (2017). Pathologic Basis of Veterinary Disease, Elsevier. [6th ed.]."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1159\/000046186","article-title":"Sieve plugs in fenestrae of glomerular capillaries\u2014Site of the filtration barrier?","volume":"170","author":"Rostgaard","year":"2002","journal-title":"Cells Tissues Organs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1007\/s10439-011-0429-8","article-title":"Endothelial glycocalyx: Permeability barrier and mechanosensor","volume":"40","author":"Curry","year":"2012","journal-title":"Ann. Biomed. Eng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/ar.1092200306","article-title":"The anionic matrix at the rat glomerular endothelial surface","volume":"220","author":"Avasthi","year":"1988","journal-title":"Anat. Rec."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1083\/jcb.98.4.1591","article-title":"Identification and characterization of podocalyxin\u2014The major sialoprotein of the renal glomerular epithelial cell","volume":"98","author":"Kerjaschki","year":"1984","journal-title":"J. Cell. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0891-6632(91)90063-U","article-title":"Loss of sulfated carbohydrate from the glomerular podocyte as a cause of albuminuria in experimental diabetic rats: Ultrastructural histochemical study","volume":"5","author":"Ina","year":"1991","journal-title":"J. Diabet. Complications."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1007\/s00467-010-1725-5","article-title":"Role of the podocyte in proteinuria","volume":"26","author":"Menzel","year":"2011","journal-title":"Pediatr. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/ki.2012.360","article-title":"Hantavirus infection: An emerging infectious disease causing acute renal failure","volume":"83","author":"Zeier","year":"2013","journal-title":"Kidney Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9811","DOI":"10.1128\/JVI.00568-11","article-title":"Pathogenic old world hantaviruses infect renal glomerular and tubular cells and induce disassembling of cell\u2013to\u2013cell contacts","volume":"85","author":"Grouls","year":"2011","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"19117","DOI":"10.1038\/s41598-020-76050-0","article-title":"Glomerular filtration barrier dysfunction in a self\u2013limiting, RNA virus\u2013induced glomerulopathy resembles findings in idiopathic nephrotic syndromes","volume":"10","author":"Nusshag","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/clinids\/13.1.97","article-title":"Mechanisms of disease in Hantavirus infection: Pathophysiology of hemorrhagic fever with renal syndrome","volume":"13","author":"Cosgriff","year":"1991","journal-title":"Rev. Infect. Dis."},{"key":"ref_21","first-page":"907","article-title":"In vivo enzymatic removal of alpha 2\u2013\u2013>6\u2013linked sialic acid from the glomerular filtration barrier results in podocyte charge alteration and glomerular injury","volume":"74","author":"Gelberg","year":"1996","journal-title":"Lab. Invest."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1097\/01.ASN.0000072742.02714.6E","article-title":"Glomerular size and charge selectivity in the mouse after exposure to glucosaminoglycan\u2013degrading enzymes","volume":"14","author":"Jeansson","year":"2003","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"F111\u20136","DOI":"10.1152\/ajprenal.00173.2005","article-title":"Morphological and functional evidence for an important role of the endothelial cell glycocalyx in the glomerular barrier","volume":"290","author":"Jeansson","year":"2006","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Meuwese, M.C., Broekhuizen, L.N., Kuikhoven, M., Heeneman, S., Lutgens, E., Gijbels, M.J., Nieuwdorp, M., Peutz, C.J., Stroes, E.S., and Vink, H. (2010). Endothelial surface layer degradation by chronic hyaluronidase infusion induces proteinuria in apolipoprotein E\u2013deficient mice. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014262"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1016\/j.ajpath.2013.01.049","article-title":"Glomerular endothelial surface layer acts as a barrier against albumin filtration","volume":"182","author":"Dane","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1073\/pnas.76.3.1303","article-title":"Presence of heparan sulfate in the glomerular basement membrane","volume":"76","author":"Kanwar","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4493","DOI":"10.1073\/pnas.76.9.4493","article-title":"Isolation of glycosaminoglycans (heparan sulfate) from glomerular basement membranes","volume":"76","author":"Kanwar","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1083\/jcb.86.2.688","article-title":"Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion","volume":"86","author":"Kanwar","year":"1980","journal-title":"J. Cell Biol."},{"key":"ref_29","first-page":"290","article-title":"Distribution of sulfated glycosaminoglycans in the glomerular basement membrane and mesangial matrix","volume":"31","author":"Kanwar","year":"1983","journal-title":"Eur. J. Cell. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Thakkar, N., Yadavalli, T., Jaishankar, D., and Shukla, D. (2017). Emerging Roles of Heparanase in Viral Pathogenesis. Pathogens, 6.","DOI":"10.3390\/pathogens6030043"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1681\/ASN.2007111205","article-title":"Adriamycin alters glomerular endothelium to induce proteinuria","volume":"20","author":"Jeansson","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12967-015-0481-5","article-title":"Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients","volume":"13","author":"Rahbar","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1161\/CIRCULATIONAHA.106.684852","article-title":"Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia","volume":"116","author":"Rehm","year":"2007","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1369\/0022155420937087","article-title":"Heparanase\u2013enhanced Shedding of Syndecan\u20131 and Its Role in Driving Disease Pathogenesis and Progression","volume":"68","author":"Rangarajan","year":"2020","journal-title":"J. Histochem. Cytochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.matbio.2011.10.001","article-title":"Molecular functions of syndecan\u20131 in disease","volume":"31","author":"Teng","year":"2012","journal-title":"Matrix Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"ofu027","DOI":"10.1093\/ofid\/ofu027","article-title":"Endothelial activation and repair during hantavirus infection: Association with disease outcome","volume":"1","author":"Thunberg","year":"2014","journal-title":"Open Forum Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"CKD\u2013EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"575047","DOI":"10.3389\/fimmu.2020.575047","article-title":"Increased Plasma Heparanase Activity in COVID\u201319 Patients","volume":"11","author":"Buijsers","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Libraty, D.H., M\u00e4kel\u00e4, S., Vlk, J., Hurme, M., Vaheri, A., Ennis, F.A., and Mustonen, J. (2012). The degree of leukocytosis and urine GATA\u20133 mRNA levels are risk factors for severe acute kidney injury in Puumala virus nephropathia epidemica. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035402"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.3389\/fimmu.2018.02098","article-title":"Neutrophil Activation in Acute Hemorrhagic Fever with Renal Syndrome Is Mediated by Hantavirus\u2013Infected Microvascular Endothelial Cells","volume":"9","author":"Strandin","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1681\/ASN.V133630","article-title":"A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression","volume":"13","author":"Saleem","year":"2002","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real\u2013time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1093\/ndt\/gfp182","article-title":"Regulation of glomerular heparanase expression by aldosterone, angiotensin II and reactive oxygen species","volume":"24","author":"Waanders","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/nrneph.2017.6","article-title":"Heparanase: Roles in cell survival, extracellular matrix remodelling and the development of kidney disease","volume":"13","author":"Rabelink","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/ki.1979.130","article-title":"Pathophysiology of Tamm\u2013Horsfall protein","volume":"16","author":"Hoyer","year":"1979","journal-title":"Kidney Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"c115","DOI":"10.1159\/000213899","article-title":"Tubular proteinuria and glomerular filtration 6 years after puumala hantavirus\u2013induced acute interstitial nephritis","volume":"112","author":"Miettinen","year":"2009","journal-title":"Nephron Clin. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1038\/sj.ki.5000334","article-title":"Ten\u2013year prognosis of Puumala hantavirus\u2013induced acute interstitial nephritis","volume":"69","author":"Miettinen","year":"2006","journal-title":"Kidney Int."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/sj.ki.5002337","article-title":"Heparanase in glomerular diseases","volume":"72","author":"Rops","year":"2007","journal-title":"Kidney Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00005-009-0061-6","article-title":"The role of heparanase in diseases of the glomeruli","volume":"58","author":"Szymczak","year":"2010","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Shafat, I., Ilan, N., Zoabi, S., Vlodavsky, I., and Nakhoul, F. (2011). Heparanase levels are elevated in the urine and plasma of type 2 diabetes patients and associate with blood glucose levels. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017312"},{"key":"ref_51","unstructured":"H\u00e4gele, S. (2018). Functional Consequences of Old World Hantavirus Infection in Human Renal Cells. [Ph.D. Thesis, Heidelberg University]."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.virusres.2018.11.015","article-title":"Virus\u2013 and cell type\u2013specific effects in orthohantavirus infection","volume":"260","author":"Nusshag","year":"2019","journal-title":"Virus Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1021\/bi0356552","article-title":"Inflammatory Cytokines and Fatty Acids Regulate Endothelial Cell Heparanase Expression","volume":"43","author":"Chen","year":"2004","journal-title":"Biochemistry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/infdis\/173.1.38","article-title":"Elevated Plasma Levels of Tumor Necrosis Factor (TNF)\u2013\u03b1, Soluble TNF Receptors, Interleukin (IL)\u20136, and IL\u201310 in Patients with Hemorrhagic Fever with Renal Syndrome","volume":"173","author":"Linderholm","year":"1996","journal-title":"J. Infec. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"659013","DOI":"10.3389\/fmed.2021.659013","article-title":"Glomerular Endothelial Cell Crosstalk With Podocytes in Diabetic Kidney Disease","volume":"8","author":"Mahtal","year":"2021","journal-title":"Front. Med."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/3\/450\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:25:08Z","timestamp":1760135108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/3\/450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,22]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["v14030450"],"URL":"https:\/\/doi.org\/10.3390\/v14030450","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,22]]}}}