Pathogenesis and Host Response in Syrian Hamsters following Intranasal Infection with Andes Virus

• DOI: 10.1371/journal.ppat.1002426
• Publication Date: 2011-12-15T21:55:05Z
• Authors: David Safronetz; Marko Zivcec; Rachel LaCasse; Friederike Feldmann; Rebecca Rosenke; Dan Long; Elaine Haddock; Douglas Brining; Donald Gardner; Heinz Feldmann; Hideki Ebihara
• Keywords: Pathogenesis; Hantavirus pulmonary syndrome; Hantavirus Infection

Hantavirus pulmonary syndrome (HPS), also referred to as hantavirus cardiopulmonary (HCPS), is a rare but frequently fatal disease caused by New World hantaviruses. In humans HPS associated with severe edema and cardiogenic shock; however, the pathogenesis of this remains unclear largely due lack suitable animal models for study progression. we monitored clinical, virological, pathophysiological parameters host immunological responses decipher pathological factors events in lethal Syrian hamster model following intranasal inoculation Andes virus. Transcriptional profiling gene demonstrated suppression innate immune most organs analyzed during early stage infection, except lung which had low level activation several pro-inflammatory genes. During phase virus established systemic infection hamsters, viral antigen readily detectable endothelium majority tissues 7–8 days post-inoculation. Despite wide-spread histological analysis confirmed abnormalities were almost exclusively found lungs. Immediately preceding clinical signs disease, intense Th1/Th2 observed lungs well heart, not peripheral organs, suggesting that localized immune-modulations paramount pathogenesis. Throughout course strong regulatory T-cell was noted hypothesized be basis aberrant activations. The unique comprehensive monitoring increases our understanding immuno-pathogenesis will facilitate development treatment strategies targeting deleterious responses.