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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Chimeric flavivirus causes vascular leakage and bone marrow suppression in a mouse model
Takeshi Kurosu1, Keiko Hanabara2, Azusa Asai2
1Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, 565-0871, Japan; Department of Virology I, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo, 208-0011, Japan.
Abstract:
Previously, we demonstrated the utility of a recombinant chimeric flavivirus (DV2ChimV), which carries the premembrane (prM) and envelope (E) genes of a type 2 DENV clinical (Thai) isolate on a backbone of Japanese encephalitis virus, for evaluating the protective efficacy of antidengue envelope antibodies both in vitro and in vivo. Here, to assess the potential use of this model for pathological studies, we aimed to characterize interferon-α/β-γ-receptor double-knockout mice (IFN-α/β/γR dKO mice) infected with DV2ChimV. Vascular leakage and bone marrow suppression are unique features of severe dengue. In the current model, DV2ChimV caused vascular leakage in the liver and intestine at the moribund stage. High levels of virus were detected in the bone marrow, and strong bone marrow suppression (i.e., disappearance of megakaryocytes and erythroblastic islets) was observed. These observations suggest that the DV2ChimV-infected mouse model mimics the vascular leakage and bone marrow suppression observed in human cases.

