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

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

doi:10.1016/j.bbrc.2023.04.003

Cited by 1 publication

(2 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MMP-8 was suspected to be the most important effector that leads to vascular leakage because it was found to be increased commonly in the liver and small intestine of DV3P12/08-infected IFN-α/β/γR KO mice ( Kurosu et al, 2023a ). Neutrophils are considered a major source of MMP-8.…”

Section: Resultsmentioning

confidence: 99%

“… Sarathy et al (2015) reported a model using the DENV-3 C0360/94 strain in AG129 mice. Furthermore, we reported another model using the DENV-3 P12/08 (DV3P12/08) clinical isolate in C57/BL6 mice lacking IFN-α/β and IFN-γ receptors (IFN-α/β/γR KO mice) ( Phanthanawiboon et al, 2016 ; Kurosu et al, 2023b ), as well as a model with a chimeric flavivirus ( Kurosu et al, 2020 , 2023a ). Zellweger et al (2010) also developed a model using the DENV-2S221 strain in A129 mice.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mice, myeloid cells, and dengue: a new model for unraveling vascular leakage mysteries

Kurosu,

Sakai,

Ami

et al. 2024

Front. Microbiol.

Self Cite

View full text Add to dashboard Cite

IntroductionSevere dengue is thought to be caused by an excessive host immune response.MethodsTo study the pathogenesis of severe dengue, we developed a novel model using LysM Cre+Ifnarflox/flox mice carrying depleted Ifnar expression only in subsets of murine myeloid cells.ResultsAlthough dengue virus (DENV) clinical isolates were not virulent in LysM Cre+Ifnarflox/flox mice, mouse-adapted DV1-5P7Sp and DV3P12/08P4Bm, which were obtained by passaging the spleen or bone marrow of mice, demonstrated 100% lethality with severe vascular leakage in the liver and small intestine. DV1-5P7Sp and DV3P12/08P4Bm harbored five and seven amino acid substitutions, respectively. Infection also induced neutrophil infiltration in the small intestine, and increased expression of IL-6 and MMP-8 and blockade of TNF-α signaling protected the mice, as demonstrated in a previous severe dengue mouse model using C57/BL6 mice lacking both IFN-α/β and IFN-γ receptors. Notably, the new models with DV1-5P7Sp and DV3P12/08P4Bm showed an increased proliferative capacity of the adapted viruses in the thymus and bone marrow.DiscussionThese observations suggest that myeloid cell infection is sufficient to trigger cytokine storm-induced vascular leakage. This model can refine the factors involved in the pathology of severe dengue leading to vascular leakage.

show abstract

Section: Resultsmentioning

confidence: 99%