A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters

Abstract

Hantavirus, the hemorrhagic causative agent of two clinical diseases, is found worldwide with variation in severity, incidence and mortality. The most lethal hantaviruses are found on the American continent where the most prevalent viruses like Andes virus and Sin Nombre virus are known to cause hantavirus pulmonary syndrome. New World hantavirus infection of immunocompetent hamsters results in an asymptomatic infection except for Andes virus and Maporal virus; the only hantaviruses causing a lethal disease in immunocompetent Syrian hamsters mimicking hantavirus pulmonary syndrome in humans. Hamsters, immunosuppressed with dexamethasone and cyclophosphamide, were infected intramuscularly with different New World hantavirus strains (Bayou virus, Black Creek Canal virus, Caño Delgadito virus, Choclo virus, Laguna Negra virus, and Maporal virus). In the present study, we show that immunosuppression of hamsters followed by infection with a New World hantavirus results in an acute disease that precisely mimics both hantavirus disease in humans and Andes virus infection of hamsters. Infected hamsters showed specific clinical signs of disease and moreover, histological analysis of lung tissue showed signs of pulmonary edema and inflammation within alveolar septa. In this study, we were able to infect immunosuppressed hamsters with different New World hantaviruses reaching a lethal outcome with signs of disease mimicking human disease. Hemorrhagic fever viruses have become of much greater importance in recent years. The more prominent presence of these viruses in a day-to-day setting and their impact on global health has had a positive impact on studying these viruses. Resolving their disease mechanisms and ways to intervene in their replication and associated health burden will stay a challenge for the upcoming decades. This challenge also counts for hantavirus, an emerging zoonosis. No vaccine or antiviral treatment is WHO prequalified or has shown to elicit a good protective or therapeutic antiviral response in humans. One of the main reasons is the lack of good animal disease models and the research focusing on this topic. Without a representative model, it is difficult to investigate new potential drugs. Within this setting we focused on establishing a disease model for the most prominent New World hantaviruses.