Chimeric flavivirus causes vascular leakage and bone marrow suppression in a mouse model

Takeshi Kurosu; Keiko Hanabara; Azusa Asai; Sabar Pambudi; Supranee Phanthanawiboon; Magot Diata Omokoko; Yusuke Sakai; Tadaki Suzuki; Kazuyoshi Ikuta

doi:10.1016/j.bbrc.2023.04.003

Chimeric flavivirus causes vascular leakage and bone marrow suppression in a mouse model

Biochem Biophys Res Commun. 2023 Jun 4:659:54-61. doi: 10.1016/j.bbrc.2023.04.003. Epub 2023 Apr 5.

Authors

Takeshi Kurosu¹, Keiko Hanabara², Azusa Asai², Sabar Pambudi², Supranee Phanthanawiboon², Magot Diata Omokoko², Yusuke Sakai³, Tadaki Suzuki³, Kazuyoshi Ikuta²

Affiliations

¹ Research 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. Electronic address: kurosu@niid.go.jp.
² Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, 565-0871, Japan.
³ Department of Pathology, National Institute of Infectious Diseases, Tokyo, 208-0011, Japan.

PMID: 37037066
DOI: 10.1016/j.bbrc.2023.04.003

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.

Keywords: Bone marrow suppression; Dengue virus; Flavivirus; Hemorrhagic fever; Mouse model; Vascular leakage.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral
Bone Marrow / pathology
Dengue Virus*
Dengue*
Flavivirus*
Humans
Mice
Mice, Knockout

Substances

Antibodies, Viral