Consumptive coagulopathy of severe yellow fever occurs independently of hepatocellular tropism and massive hepatic injury
Adam L. Bailey, Liang‐I Kang, Luiz Gonzaga Francisco de Assis Barros D’Elia Zanella, Cássia Gisele Terrassani Silveira, Chung-Chou H. Chang, Lander Foquet, Greg Bial, Broc T. McCune, Amaro Nunes Duarte‐Neto, Archana Thomas, Hans-Peter Raué, Kathleen Byrnes, Esper G. Kallás, Mark K. Slifka, Michael Diamond
Abstract
mice engrafted with human hepatocytes (hFRG mice) and rhesus macaques using a highly pathogenic African YFV strain. YFV infection of macaques and hFRG mice caused substantial hepatocyte infection, liver damage, and coagulopathy as defined by virological, clinical, and pathological criteria. However, only macaques developed a consumptive coagulopathy whereas YFV-infected hFRG mice did not. Thus, infection of cell types other than hepatocytes likely contributes to the consumptive coagulopathy associated with severe YF in primates and humans. These findings expand our understanding of viral hemorrhagic disease and associated coagulopathy and suggest directions for clinical management of severe YF cases.