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Interferons Induce STAT1-Dependent Expression of Tissue Plasminogen Activator, a Pathogenicity Factor in Puumala Hantavirus Disease
Univ Helsinki, Fac Med, Dept Virol, POB 21,Haartmaninkatu 3, FI-00014 Helsinki, Finland..
Univ Helsinki, Fac Med, Dept Virol, POB 21,Haartmaninkatu 3, FI-00014 Helsinki, Finland..
Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.;Tampere Univ Hosp, Dept Internal Med, Tampere, Finland..
Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.;Tampere Univ Hosp, Dept Internal Med, Tampere, Finland..
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2016 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 213, no 10, 1632-1641 p.Article in journal (Refereed) PublishedText
Abstract [en]

Hantaviruses are zoonotic viruses that show various degrees of vasculopathy in humans. In this study, we analyzed the regulation of 2 fibrinolytic parameters, tissue plasminogen activator (tPA) and its physiological inhibitor, plasminogen activator inhibitor 1 (PAI-1), in Puumala hantavirus (PUUV)-infected patients and in human microvascular endothelial cells. We detected strong upregulation of tPA in the acute phase of illness and in PUUV-infected macaques and found the tPA level to positively correlate with disease severity. The median levels of PAI-1 during the acute stage did not differ from those during the recovery phase. In concordance, hantaviruses induced tPA but not PAI-1 in microvascular endothelial cells, and the induction was demonstrated to be dependent on type I interferon. Importantly, type I and II interferons directly upregulated tPA through signal transducer and activator of transcription 1 (STAT1), which regulated tPA gene expression via a STAT1-responsive enhancer element. These results suggest that tPA may be a general factor in the immunological response to viruses.

Place, publisher, year, edition, pages
2016. Vol. 213, no 10, 1632-1641 p.
Keyword [en]
tissue plasminogen activator, interferon, STAT1, hantavirus, hemorrhagic fever, innate immunity
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:uu:diva-298407DOI: 10.1093/infdis/jiv764ISI: 000376648900016PubMedID: 26704613OAI: oai:DiVA.org:uu-298407DiVA: diva2:945925
Funder
EU, European Research Council, QLK2-CT-2002-01358
Available from: 2016-07-04 Created: 2016-07-04 Last updated: 2016-08-31Bibliographically approved

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Lundkvist, Åke
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Department of Medical Biochemistry and Microbiology
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ReferencesLink to record
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