Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis

de-Oliveira-Pinto, Luzia Maria; Gandini, Mariana; Freitas, Laís Picinini; Siqueira, Marilda Mendonça; Marinho, Cíntia Ferreira; Setúbal, Sérgio; Kubelka, Claire Fernandes; Cruz, Oswaldo Gonçalves; Oliveira, Solange Artimos de

doi:10.1590/s0074-02762012000100007

Cited by 34 publications

(24 citation statements)

References 58 publications

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“…The mast cell-derived mediator VEGF, first identified and characterized as a potent stimulator of endothelial permeability (36) and shown to be elevated in dengue patients with hemorrhagic syndrome (37,38), was also significantly elevated in infected versus control mice at day 3 postinfection. Likewise, IP-10, which was previously shown to be a strong proinflammatory marker in dengue virus-infected patients at the febrile phase (39,40), was present at elevated levels at 3 days postinfection. In-creased circulating IL-1R␣ may exert antipyretic actions in an effort to counteract the already-increased concentrations of proinflammtory cytokines, such as IL-1␤, which was shown to be elevated in dengue virus-infected patients (40) but was not part of our cytokine panel.…”

Section: Cell Tropism Of Denv-2 Col Infection In Different Organs Of mentioning

confidence: 61%

Utility of Humanized BLT Mice for Analysis of Dengue Virus Infection and Antiviral Drug Testing

Frias-Stäheli

Dorner

Marukian

et al. 2014

J Virol

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Dengue virus (DENV) is the cause of a potentially life-threatening disease that affects millions of people worldwide. The lack of a small animal model that mimics the symptoms of DENV infection in humans has slowed the understanding of viral pathogenesis and the development of therapies and vaccines. Here, we investigated the use of humanized "bone marrow liver thymus" (BLT) mice as a model for immunological studies and assayed their applicability for preclinical testing of antiviral compounds. Human immune system (HIS) BLT-NOD/SCID mice were inoculated intravenously with a lowpassage, clinical isolate of DENV-2, and this resulted in sustained viremia and infection of leukocytes in lymphoid and nonlymphoid organs. In addition, DENV infection increased serum cytokine levels and elicited DENV-2-neutralizing human IgM antibodies. Following restimulation with DENV-infected dendritic cells, in vivo-primed T cells became activated and acquired effector function. An adenosine nucleoside inhibitor of DENV decreased the circulating viral RNA when administered simultaneously or 2 days postinfection, simulating a potential treatment protocol for DENV infection in humans. In summary, we demonstrate that BLT mice are susceptible to infection with clinical DENV isolates, mount virusspecific adaptive immune responses, and respond to antiviral drug treatment. Although additional refinements to the model are required, BLT mice are a suitable platform to study aspects of DENV infection and pathogenesis and for preclinical testing of drug and vaccine candidates. IMPORTANCEInfection with dengue virus remains a major medical problem. Progress in our understanding of the disease and development of therapeutics has been hampered by the scarcity of small animal models. Here, we show that humanized mice, i.e., animals engrafted with components of a human immune system, that were infected with a patient-derived dengue virus strain developed clinical symptoms of the disease and mounted virus-specific immune responses. We further show that this mouse model can be used to test preclinically the efficacy of antiviral drugs.

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Section: Cell Tropism Of Denv-2 Col Infection In Different Organs Of mentioning

confidence: 61%

Utility of Humanized BLT Mice for Analysis of Dengue Virus Infection and Antiviral Drug Testing

Frias-Stäheli

Dorner

Marukian

et al. 2014

J Virol

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“…Basically, NS2B3 can abrogate IRF3 phosphorylation, but has no impact on NF-κB activation during DENV infection47. For NS2B3-induced inflammation, our previous work14 and others48 showed NS2B3 causes NF-κB-regulated TNF-α production. Previous works also demonstrated that NS2B3 may bind to inhibitors of κB to activate NF-κB49.…”

Section: Discussionmentioning

confidence: 98%

Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-α production by mononuclear phagocytes

Cheng

Lin

Chen

et al. 2016

Sci Rep

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Infection by the dengue virus (DENV) threatens global public health due to its high prevalence and the lack of effective treatments. Host factors may contribute to the pathogenesis of DENV; herein, we investigated the role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which is activated by DENV in mononuclear phagocytes. DENV infection selectively activates Nrf2 following nuclear translocation. Following endoplasmic reticular (ER) stress, protein kinase R-like ER kinase (PERK) facilitated Nrf2-mediated transcriptional activation of C-type lectin domain family 5, member A (CLEC5A) to increase CLEC5A expression. Signaling downstream of the Nrf2-CLEC5A interaction enhances Toll-like receptor 3 (TLR3)-independent tumor necrosis factor (TNF)-α production following DENV infection. Forced expression of the NS2B3 viral protein induces Nrf2 nuclear translocation/activation and CLEC5A expression which increases DENV-induced TNF-α production. Animal studies confirmed Nrf2-induced CLEC5A and TNF-α in brains of DENV-infected mice. These results demonstrate that DENV infection causes Nrf2-regulated TNF-α production by increasing levels of CLEC5A.

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“…107(8): 1021-1029, December 2012 Clinical and pathological evidence implicating abnormal cytokine release as the main mediator of disease and an increased risk of severe dengue disease have been described during secondary dengue virus (DENV) infections (Kurane & Ennis 1992). Indeed elevated levels of tumour necrosis factor (TNF)-α have been detected in dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) patients (Vitarana et al 1991, Hober et al 1993, Nguyen et al 2004) and the production of this cytokine was correlated with increased numbers of macrophages/monocytes (de-Oliveira-Pinto et al 2012), which are potent phagocytic cells and primary targets for DENV infection (Kangwanpong et al 1995, Jessie et al 2004. These cells express all three classes of FCγR making them especially prone to DENV entry in the form of virus-antibody immune complexes ).…”

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confidence: 99%

Environmental influences on antibody-enhanced dengue disease outcomes

Diniz

Fôro

Turiel³

et al. 2012

Mem. Inst. Oswaldo Cruz

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Because an enriched environment (EE) enhances T-cell activity and T-lymphocytes contribute to immunopathogenesis during heterologous dengue virus (DENV) infections, we hypothesised that an EE increases dengue severity. To compare single serotype (SS) and antibody-enhanced disease (AED) infections regimens, serial intraperitoneal were performed with DENV3 (genotype III) infected brain homogenate or anti-DENV2 hyperimmune serum followed 24 h later by DENV3 (genotype III) infected brain homogenate. Compared AED for which significant differences were detected between the EE and impoverished environmental (IE) groups (Kaplan-Meyer log-rank test, p = 0.0025), no significant differences were detected between the SS experimental groups (Kaplan-Meyer log-rank test, p = 0.089). Survival curves from EE and IE animals infected with the AED regimen were extended after corticoid injection and this effect was greater in the EE than in the IE group (Kaplan-Meyer log-rank test, p = 0.0162). Under the AED regimen the EE group showed more intense clinical signs than the IE group. Dyspnoea, tremor, hunched posture, ruffled fur, immobility, pre-terminal paralysis, shock and death were associated with dominant T-lymphocytic hyperplasia and presence of viral antigens in the liver and lungs. We propose that the increased expansion of these memory T-cells and serotype cross-reactive antibodies facilitates the infection of these cells by DENV and that these events correlate with disease severity in an EE

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Profile of circulating levels of IL-1Ra, CXCL10/IP-10, CCL4/MIP-1β and CCL2/MCP-1 in dengue fever and parvovirosis

Abstract: Dengue virus (DENV) and parvovirus B19 (B19V) infections

Cited by 34 publications

References 58 publications

Utility of Humanized BLT Mice for Analysis of Dengue Virus Infection and Antiviral Drug Testing

Utility of Humanized BLT Mice for Analysis of Dengue Virus Infection and Antiviral Drug Testing

Activation of Nrf2 by the dengue virus causes an increase in CLEC5A, which enhances TNF-α production by mononuclear phagocytes

Environmental influences on antibody-enhanced dengue disease outcomes

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