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

<div><p>Background</p><p>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.</p><p>Methodology/Principal findings</p><p>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.</p><p>Conclusions/ Significance</p><p>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.</p></div

Histology of lung tissue from BAYV-, BCCV- and uninfected immunosuppressed hamsters.

<p>A) Lung biopsy showing a diffuse acute inflammation. Alveoli are filled with edema, mostly polymorphic inflammatory cells and fibrin (H&E x 100; Black Creek Canal virus group). B) Lung biopsy showing severe hemorrhagic edema in the alveoli, spilling over in the bronchiolar lumen (H&E x 100; Bayou virus group) C) Lung biopsy showing normal alveolar parenchyma and bronchioles (H&E x 100; Dex-Cyp control group).</p

Survival curves of golden Syrian hamsters infected with New World hantaviruses.

<p>A) Infection with New World hantaviruses (BAYV, BCCV, CDV, SNV and ANDV) leading to a mortality rate of 100%. B) Infection with New World hantaviruses leading to a mortality rate of 75% for CHOV and 50% for LNV and MAPV. BAYV, CDV, BCCV, ANDV and SNV, Log-rank: p value <0.0001, Gehan-Breslow-Wilcoxon: p value = 0.0002; LNV and MAPV, Log-rank: p value = 0.0251, Gehan-Breslow-Wilcoxon: p value = 0.0265; and CHOV; Log-rank: p value = 0.0024, Gehan-Breslow-Wilcoxon: p value = 0.0032.</p

Dexamethasone and cyclophosphamide dosing scheme.

<p>Dexamethasone and cyclophosphamide dosing scheme.</p