Humanized mouse models to study human cell-mediated and humoral responses to dengue virus

Mathew, Anuja

doi:10.1016/j.coviro.2017.07.025

Cited by 9 publications

(7 citation statements)

References 37 publications

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“…While beyond the scope of this review, small animal models of DENV and ZIKV infection are of vital importance in pre-clinical testing of the efficacy and safety of vaccine candidates. Recent advances in this area have been comprehensively reviewed elsewhere [ 106 , 122 , 123 ].…”

Section: Exploitation Of Enhanced Type-i Ifn Responses For Effectimentioning

confidence: 99%

The Molecular Interactions of ZIKV and DENV with the Type-I IFN Response

2020

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Zika Virus (ZIKV) and Dengue Virus (DENV) are related viruses of the Flavivirus genus that cause significant disease in humans. Existing control measures have been ineffective at curbing the increasing global incidence of infection for both viruses and they are therefore prime targets for new vaccination strategies. Type-I interferon (IFN) responses are important in clearing viral infection and for generating efficient adaptive immune responses towards infection and vaccination. However, ZIKV and DENV have evolved multiple molecular mechanisms to evade type-I IFN production. This review covers the molecular interactions, from detection to evasion, of these viruses with the type-I IFN response. Additionally, we discuss how this knowledge can be exploited to improve the design of new vaccine strategies.

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Section: Exploitation Of Enhanced Type-i Ifn Responses For Effectimentioning

confidence: 99%

The Molecular Interactions of ZIKV and DENV with the Type-I IFN Response

2020

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“…Therefore, we expected to observe an increase in these T-cells in hu-NSG mice infected with CHIKV. The hu-NSG mouse model does not produce robust human T-cell responses, because the mice lack a human thymus, resulting in human T-cells that recognize mouse antigen-presenting cells as opposed to human antigen-presenting cells [ 144 ]. Studies using humanized mouse models with robust human T-cell responses, such as the BLT model, could clarify the role of these cells in CHIKV pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects

et al. 2021

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Chikungunya virus (CHIKV) is an emerging, mosquito-borne alphavirus responsible for acute to chronic arthralgias and neuropathies. Although it originated in central Africa, recent reports of disease have come from many parts of the world, including the Americas. While limiting human CHIKV cases through mosquito control has been used, it has not been entirely successful. There are currently no licensed vaccines or treatments specific for CHIKV disease, thus more work is needed to develop effective countermeasures. Current animal research on CHIKV is often not representative of human disease. Most models use CHIKV needle inoculation via unnatural routes to create immediate viremia and localized clinical signs; these methods neglect the natural route of transmission (the mosquito vector bite) and the associated human immune response. Since mosquito saliva has been shown to have a profound effect on viral pathogenesis, we evaluated a novel model of infection that included the natural vector, Aedes species mosquitoes, transmitting CHIKV to mice containing components of the human immune system. Humanized mice infected by 3–6 mosquito bites showed signs of systemic infection, with demonstrable viremia (by qRT-PCR and immunofluorescent antibody assay), mild to moderate clinical signs (by observation, histology, and immunohistochemistry), and immune responses consistent with human infection (by flow cytometry and IgM ELISA). This model should give a better understanding of human CHIKV disease and allow for more realistic evaluations of mechanisms of pathogenesis, prophylaxis, and treatments.

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“…However, due to significant drawbacks, these models did not lead to major breakthroughs in the understanding of human dengue fever. An additional aggravating factor in research on DENV infection is that previous immunity is considered a major risk factor for the development of severe hemorrhagic fever and most severe symptoms are observed at the peak of the human antiviral immune response (reviewed in [161][162][163]). Thus, humanized mouse models have become the most common models used for the study of DENV and the rapid development of new transgenic human-mouse hybrid models recently increased insights into DENV infections.…”

Section: Transgenic Humanized Mouse Models For Human-specific Bloodborne and Hepatotropic Virusesmentioning

confidence: 99%

Advances in Transgenic Mouse Models to Study Infections by Human Pathogenic Viruses

Masemann

Ludwig

Boergeling

2020

IJMS

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Medical research is changing into direction of precision therapy, thus, sophisticated preclinical models are urgently needed. In human pathogenic virus research, the major technical hurdle is not only to translate discoveries from animals to treatments of humans, but also to overcome the problem of interspecies differences with regard to productive infections and comparable disease development. Transgenic mice provide a basis for research of disease pathogenesis after infection with human-specific viruses. Today, humanized mice can be found at the very heart of this forefront of medical research allowing for recapitulation of disease pathogenesis and drug mechanisms in humans. This review discusses progress in the development and use of transgenic mice for the study of virus-induced human diseases towards identification of new drug innovations to treat and control human pathogenic infectious diseases.

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Humanized mouse models to study human cell-mediated and humoral responses to dengue virus

Cited by 9 publications

References 37 publications

The Molecular Interactions of ZIKV and DENV with the Type-I IFN Response

The Molecular Interactions of ZIKV and DENV with the Type-I IFN Response

Mosquito-bite infection of humanized mice with chikungunya virus produces systemic disease with long-term effects

Advances in Transgenic Mouse Models to Study Infections by Human Pathogenic Viruses

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