A1 Refereed original research article in a scientific journal

Interferons Induce STAT1-Dependent Expression of Tissue Plasminogen Activator, a Pathogenicity Factor in Puumala Hantavirus Disease




AuthorsStrandin T, Hepojoki J, Laine O, Makela S, Klingstrom J, Lundkvist A, Julkunen I, Mustonen J, Vaheri A

PublisherOXFORD UNIV PRESS INC

Publication year2016

JournalJournal of Infectious Diseases

Journal name in sourceJOURNAL OF INFECTIOUS DISEASES

Journal acronymJ INFECT DIS

Volume213

Issue10

First page 1632

Last page1641

Number of pages10

ISSN0022-1899

eISSN1537-6613

DOIhttps://doi.org/10.1093/infdis/jiv764(external)


Abstract
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.



Last updated on 2024-26-11 at 19:45