Immune response to orthohantaviruses

It`s a scenario that probably plays out in many households: Garden sheds are being made spring- ready, gardens are being dug up, storage areas are being cleared out. Such work raises dust - and this dust can transmit a virus that has been spreading since the 1990s, especially in Styria: The Puumala virus. It belongs to the group of hantaviruses and spreads via a rodent that roams not only in forests and meadows, but also in attics, barns or huts: the bank vole. It excretes the virus through its feces and urine, which remains infectious in dust for up to two weeks - and which humans can inhale. Styria is the hotspot for Puumala infections in Austria. About 90 percent of the cases occur in Styria, with isolated cases also in Carinthia and Burgenland. In normal years, there are an average of 25 cases in Austria - but there have also been outlier years in which more than 200 cases of the disease occurred. At first glance, this does not seem like much - insidiously, however, the disease can be very severe in some cases. The spectrum of disease forms ranges from a mild flu-like infection to "a life-threatening infection that may affect many organs of the body. Like severe courses of influenza or Covid- 19, the virus can attack the lungs, central nervous system or kidney, sending the infected to intensive care unit. Up to four percent of infections are fatal. The reason why so few are so severely affected is being clarified as part of the research project "Immune Response against Orthohantaviruses. This project will be carried out together with Florian Krammer a renown virologist leading a research laboratory at the Icahn School of Medicine at Mount Sinai in New York City. The project aims to discover specific therapies against the virus as well as potential vaccinations. The basis of specific therapy and vaccination is always to find a well-matched antibody against hantaviruses. This antibody search is one of the central points of the project funded by the FWF - Schrödinger.

Springtime in Styria, Austria - garden sheds are cleaned, yards are dug up, storage areas are cleared. What many don't realize: this dust can carry a dangerous virus - the Puumala virus. It belongs to the hantavirus family and is spread by the bank vole, a rodent found not only in forests and fields but also in attics, barns, and sheds. The virus is excreted through the animal's urine and feces, can remain infectious in dust for up to two weeks, and may infect humans when inhaled. Styria is the main hotspot for Puumala virus infections in Austria - around 90 percent of cases occur here. While the annual average is about 25 reported cases, certain years have seen over 200. Though many infections are mild, some can lead to severe or even life-threatening illness. The virus can attack the lungs, kidneys, or brain, similar to serious cases of influenza or COVID-19. The mortality rate can reach up to four percent. One of the key questions of this research project is why some individuals experience severe outcomes while others do not. The goal of this FWF-funded project is to better understand the immune response to Puumala virus infection. In collaboration with leading virologist Florian Krammer from the Icahn School of Medicine at Mount Sinai in New York, researchers are analyzing the antibody responses of infected patients. Blood samples were collected from 23 hospitalized individuals at four stages of the disease - from early acute illness to late recovery. The findings reveal that the immune system mounts a strong response early in the infection. Remarkably, several months after illness, additional cross-reactive antibodies emerge that can recognize a broader range of hantaviruses - including more dangerous strains. These insights mark an important step toward the development of targeted therapies and potential vaccines against hantaviruses. Especially promising are the broadly neutralizing antibodies that appear during late recovery - they could form the basis for therapeutic monoclonal antibodies, a type of highly specific antiviral treatment. Furthermore, shifts in antibody subtypes suggest that remnants of the virus may persist in the body for months - a factor that could be critical for future diagnostic and treatment strategies. This project not only advances our understanding of a neglected viral threat but also paves the way for effective prevention and therapy - originating in Styria, with international scientific collaboration.