Chimeric flavivirus causes vascular leakage and bone marrow suppression in a mouse model
Chimeric flavivirus causes vascular leakage and bone marrow suppression in a mouse model
复制标题
嵌合黄病毒在小鼠模型中引起血管渗漏和骨髓抑制
DOI：
10.1016/j.bbrc.2023.04.003
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Kazuyoshi Ikuta
中科院分区：
文献类型：
--
作者：
Takeshi Kurosu;Keiko Hanabara;Azusa Asai;Sabar Pambudi;Supranee Phanthanawiboon;Magot Diata Omokoko;Yusuke Sakai;Tadaki Suzuki;Kazuyoshi Ikuta
在此之前，我们证明了重组嵌合黄病毒（DV2ChimV）在日本脑炎病毒主干上携带DENV临床（泰国）2型分离物的膜前（prM）和包膜(E)基因，用于评估体外和体内抗登革热包膜抗体的保护作用。在这里，为了评估该模型在病理研究中的潜在应用，我们旨在表征感染了DV2ChimV的干扰素-α/β - γ受体双敲除小鼠（IFN-α/β/γR dKO小鼠）。血管渗漏和骨髓抑制是重症登革热的独特特征。在目前的模型中，DV2ChimV在死亡阶段引起肝脏和肠道血管渗漏。在骨髓中检测到高水平的病毒，并观察到强烈的骨髓抑制（即巨核细胞和红母细胞的消失）。这些观察结果表明，dv2chimv感染的小鼠模型模拟了在人类病例中观察到的血管渗漏和骨髓抑制。
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 bothin vitroandin 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.