Viral haemorrhagic fevers in Europe: Impact of Puumala Hantavirus infection on primary haemostasis

 

PI: Waltraud Schrottmaier
Funded by: Anniversary Fund of the Austrian National Bank (OeNB18450)
Funding period: 12/2020-05/2022

 

Recent severe outbreaks such as the West African Ebola virus epidemic with over 11.000 fatalities have put increased attention on viral haemorrhagic fevers (VHF). However, while VHFs such as Dengue and Ebola that mostly occur in Africa and Asia are well-known, awareness of Hantavirus-induced VHFs occurring in Europe and the Americas is low even though their mortality can reach 40%.

With about 2% mortality, the European Puumala Hantavirus (PUUV) is the mildest of the closely-related Hantaviruses, making PUUV the ideal candidate to study underlying mechanisms common to Hantavirus-induced VHFs. PUUV infection causes fever, temporary kidney failure and thrombocytopenia, leading to gastrointestinal bleedings but also to a higher risk for thrombosis.

Studying this double-edged effect on primary haemostasis and the resulting knowledge will help in the treatment of Hantavirus-infected VHF patients in order to limit potentially life-threatening haemorrhagic and thrombotic complications.

VHFs such as PUUV infection-caused Nephropathia epidemica (NE) are characterized by impaired haemostasis. As the cellular mediators of haemostasis, platelets are of pivotal importance for maintaining vascular integrity. Thus, low platelet counts and decreased platelet function - as occurring during acute NE - are associated with increased risk for bleeding.

Although platelets play a central role in PUUV-induced haemorrhagic fever, it is currently unknown how PUUV infection causes thrombocytopenia and platelet dysfunction. Therefore, we aim to elucidate how infection with PUUV modulates platelet activation and platelet production.

We speculate that systemic PUUV infection activates platelets and induces endothelial adhesion and sequestration in capillary-rich organs, thereby reducing the number of circulating platelets. Further, PUUV infection may reduce the production of platelets by compromising maturation and/or differentiation of their progenitor cells in the bone marrow.

In order to investigate this, we are screening the blood of NE patients and performing in vitro experiments to evaluate the direct and indirect effects of PUUV on platelet production, function and activation.

We are convinced that the results of the study will be interesting for physicians and basic researchers alike as they will add significant knowledge to a more comprehensive view of the pathogenesis of Hantavirus-induced haemorrhagic fevers.