Japanese encephalitis virus induces vasodilation and severe lethality in adult and aged AG129 mice lacking alpha, beta and gamma interferon receptors

Siddqui, Gazala; Yadav, Naveen; Vishwakarma, Preeti; Thomas, Jolly; Khatri, Ritika; Kumar, Amit; Tripathi, Aarti; Pramod, R. Kumar; Vrati, Sudhanshu; Samal, Sweety

doi:10.1016/j.virusres.2022.198884

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…Previous studies have used type-I interferon receptor-knockout mice with either C57BL/6 or 129 backbone, STAT-1 knockout mice and mice treated with cyclophosphamide to establish infection models of human pathogenic orthonairoviruses such as CCHFV and Dugbe virus [14][15][16]. Here, we have demonstrated that AG129 mice, which are widely utilized in the field of flavivirus research as lethal infection models [34][35][36][37][38], can also be utilized for establishing a model of tick-borne orthonairovirus infections. Because YEZV was isolated from a human patient using AG129 mice that showed swelling of the spleen [12], AG129 mice was our first choice for establishing a mouse model of YEZV infection.…”

Section: Plos Pathogensmentioning

confidence: 78%

Establishment of a lethal mouse model of emerging tick-borne orthonairovirus infections

Ariizumi,

Tabata,

Itakura

et al. 2024

PLoS Pathog

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Emerging and reemerging tick-borne orthonairovirus infections (family Nairoviridae), which are genetically distinct from Crimean-Congo hemorrhagic fever virus, have been recently reported in East Asia. Here, we have established a mouse infection model using type-I/II interferon receptor-knockout mice (AG129) both for a better understanding the pathogenesis of these infections and validation of antiviral agents using Yezo virus (YEZV), a novel virus causing febrile illnesses associated with tick bites in Japan and China. YEZV-inoculated AG129 mice developed hepatitis with body weight loss and died by 6 days post infection. Blood biochemistry tests showed elevated liver enzyme levels, similar to YEZV-infected human patients. AG129 mice treated with favipiravir survived lethal YEZV infection, demonstrating the anti-YEZV effect of this drug. The present mouse model will help us better understand the pathogenicity of the emerging tick-borne orthonairoviruses and the development of specific antiviral agents for their treatment.

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Section: Plos Pathogensmentioning

confidence: 78%

Establishment of a lethal mouse model of emerging tick-borne orthonairovirus infections

Ariizumi,

Tabata,

Itakura

et al. 2024

PLoS Pathog

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“…In our recent study, we found the Japanese encephalitis virus could significantly alter the disease pathogenesis in the aged AG129 murine infection model ( Siddqui et al., 2022 ) as compared to adult mice. In the present study, we have shown that aged AG129 mice are highly susceptible to DENV-1 (NR-3785, isolated in 1984 from humans in the Philippines), DENV-2 (NR-15247, derived from the existing New Guinea C (NGC; New Guinea/NGC/1944) strain), DENV-3 (Indian clinical isolate), and DENV-4 (NR-48801,703-4, isolated from humans in 1994 in Thailand) serotypes.…”

Section: Introductionmentioning

confidence: 99%

Aged AG129 mice support the generation of highly virulent novel mouse-adapted DENV (1-4) viruses exhibiting neuropathogenesis and high lethality

Siddqui,

Vishwakarma,

Saxena

et al. 2024

Virus Research

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Dengue virus infection in mice induces bone marrow myeloid cell differentiation and generates Ly6Glow immature neutrophils with modulated functions

Duggal,

Rawat,

Siddqui

et al. 2023

Journal of Leukocyte Biology

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While neutrophil activation during dengue virus (DV) infection is known, the effect of DV infection on neutrophil biogenesis has not been studied. We demonstrate that DV serotype-2 (DV2) induces the differentiation of mice progenitor cells ex vivo towards the CD11b + Ly6C + Ly6G+ granulocyte population. We further observed an expansion of CD11b + Ly6CintLy6Glow myeloid cells in the bone marrow of DV2-infected AG129 mice with low CXCR2 expression, implying immature population. Additionally, DV2 alone could induce the differentiation of promyelocyte cell line HL-60 into neutrophil-like cells (NLCs) as evidenced by increased expression of CD10, CD66b, CD16, CD11b, and CD62L, corroborating the preferential shift towards neutrophil differentiation by DV2 in the mouse model of dengue infection. The functional analysis showed that DV2-induced NLCs exhibited reduced phagocytic activity and enhanced NETosis as evidenced by the increased production of myeloperoxidase (MPO), citrullinated-Histones, extracellular DNA, and superoxide. These NLCs lose their ability to proliferate irreversibly and undergo arrest in the G0-G1 phase of the cell cycle. Further studies show that MPO-mediated signaling operating through the ROS axis may be involved in DV2-induced proliferation and differentiation of bone marrow cells as ABAH, an MPO inhibitor, limits cell proliferation in vitro and ex vi vo, affects the cell cycle, and reduces ROS production. Additionally, MPO inhibitor reduced NETosis and vascular leakage in DV2-infected AG129 mice. Our study thus provides evidence that DV2 can accelerate the differentiation of bone marrow progenitor cells into neutrophils through MPO and modulate their functions.

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Japanese encephalitis virus induces vasodilation and severe lethality in adult and aged AG129 mice lacking alpha, beta and gamma interferon receptors

Cited by 3 publications

References 43 publications

Establishment of a lethal mouse model of emerging tick-borne orthonairovirus infections

Establishment of a lethal mouse model of emerging tick-borne orthonairovirus infections

Aged AG129 mice support the generation of highly virulent novel mouse-adapted DENV (1-4) viruses exhibiting neuropathogenesis and high lethality

Dengue virus infection in mice induces bone marrow myeloid cell differentiation and generates Ly6Glow immature neutrophils with modulated functions

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