| 1. |
- Hepojoki, Satu, et al.
(author)
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Competitive Homogeneous Immunoassay for Rapid Serodiagnosis of Hantavirus Disease
- 2015
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In: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 53:7, s. 2292-2297
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Journal article (peer-reviewed)abstract
- In this study, we describe a competitive homogeneous immunoassay that makes use of Forster resonance energy transfer (FRET) in rapid detection of pathogen-specific antibodies. The assay principle is based on competition between a monoclonal antibody (MAb) and serum antibodies to a given antigen. In the assay, named competitive FRET immunoassay (CFRET-IA), the FRET signal is induced if MAb carrying a donor label binds to an acceptor-labeled antigen. Specific antibodies in serum compete for antigen binding, resulting in reduced FRET signal. The proof-of-principle for the assay was obtained using donor-labeled Puumala virus nucleocapsid protein (PUUV-N) and acceptor-labeled anti-PUUV-N MAb. The assay was evaluated by analyzing 329 clinical samples comprising 101 from individuals with acute PUUV infection, 42 from individuals with past infection, and 186 from individuals with PUUV-seronegative sera, and the results were compared to those of reference tests. The rapid serodiagnostic test we introduced herein performed with 100% sensitivity and 99% specificity for diagnosing acute hantavirus disease.
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| 2. |
- Ling, Jiaxin, et al.
(author)
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Evolution and postglacial colonization of Seewis hantavirus with Sorex araneus in Finland
- 2018
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In: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 57, s. 88-97
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Journal article (peer-reviewed)abstract
- Hantaviruses have co-existed with their hosts for millions of years. Seewis virus (SWSV), a soricomorph-borne hantavirus, is widespread in Eurasia, ranging from Central Siberia to Western Europe. To gain insight into the phylogeography and evolutionary history of SWSV in Finland, lung tissue samples of 225 common shrews (Sorex araneus) trapped from different parts of Finland were screened for the presence of SWSV RNA. Forty-two of the samples were positive. Partial small (S), medium (M) and large (L) segments of the virus were sequenced, and analyzed together with all SWSV sequences available in Genbank. The phylogenetic analysis of the partial S-segment sequences suggested that all Finnish SWSV strains shared their most recent common ancestor with the Eastern European strains, while the L-segment suggested multiple introductions. The difference between the Land S-segment phylogenies implied that reassortment events play a role in the evolution of SWSV. Of the Finnish strains, variants from Eastern Finland occupied the root position in the phylogeny, and had the highest genetic diversity, supporting the hypothesis that SWSV reached Finland first form the east. During the spread in Finland, the virus has formed three separate lineages, identified here by correlation analysis of genetic versus geographic distance combined with median-joining network analysis. These results support the hypothesis that Finnish SWSV recolonized Finland with its host, the common shrew, from east after the last ice age 12,000-8000 years ago, and then subsequently spread along emerging land bridges towards west or north with the migration and population expansion of its host.
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| 3. |
- Sironen, Tarja, et al.
(author)
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Fatal Puumala Hantavirus Disease : Involvement of Complement Activation and Vascular Leakage in the Pathobiology
- 2017
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In: Open Forum Infectious Diseases. - : Oxford University Press. - 2328-8957. ; 4:4
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Journal article (peer-reviewed)abstract
- The case-fatality rate of hantavirus disease depends strongly on the causative hantavirus, ranging from 0.1% to 40%. However, the pathogenesis is not fully understood, and at present no licensed therapies exist. We describe fatal cases caused by Puumala hantavirus indicating involvement of complement activation and vascular leakage.
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| 4. |
- Strandin, Tomas, et al.
(author)
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Interferons Induce STAT1-Dependent Expression of Tissue Plasminogen Activator, a Pathogenicity Factor in Puumala Hantavirus Disease
- 2016
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 213:10, s. 1632-1641
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Journal article (peer-reviewed)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.
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