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IRF-3/5/7-Independent Antiviral Immunity

IRF-3/5/7-Independent Antiviral Immunity
IRF-3/5/7-独立的抗病毒免疫
批准号:
9029196
负责人:
Sujan Shresta
金额:
$44.25万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-03-01 至 2020-02-29

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中文摘要
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英文摘要
 DESCRIPTION (provided by applicant): Dengue virus (DENV) is the causative agent of dengue fever (DF) and the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), the most prevalent mosquito-borne viral diseases worldwide. Signaling by type I interferon (IFN) is critical for protecting the host during DENV infection. Although the absence of one or multiple of transcription factors IRF-3, IRF-5, and IRF-7 in mice is sufficient to increase susceptibility to infection with various viruses, mice lacking all three (TKO) remain resistant to DENV challenge that is lethal in type I IFN receptor-deficient mice. This indicates the presence of an IRF-3, IRF-5, and IRF-7-independent (hereafter termed IRF-3/5/7-independent) mechanism against DENV that is required for host protection. Identification of this pathway is important because the transcriptional regulation of type IFN and interferon-stimulated gene (ISG) response for antiviral immunity is not fully understood, as new studies reveal that multiple transcription factors exist to regulate type I IFN production and ISG expression in a cell-specific host species-specific, time-specific, or virus-specific manner. In the proposed studies, we seek to define the transcription factors that are responsible for protection against DENV despite the absence of major transcription factors IRF-3, IRF-5, and IRF-7 in both mouse and human macrophages. Our preliminary data suggest that the IRF-3/5/7-independent pathway is type I IFN- dependent. We will test the hypothesis that in the absence of IRF-3, IRF-5, and IRF-7, type I IFN and ISG responses still occur to protect against DENV, potentially through activities of IRF-1, ELF4, or other transcription factors with previously unknown relation to antiviral immunity. The Specific Aims are: 1. To investigate the role of type I IFN signaling in the IRF-3/5/7-independent mechanism of protection against DENV infection. 2. To evaluate the role of IRF-1 and ELF4 in the IRF-3/5/7-independent pathway. 3. To identify novel transcription factors that regulate the IRF-3/5/7-independent pathway.
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Maternal Antibody-Mediated Enhancement of Dengue Pathogenesis
Development of a Replicon RNA-based Vaccine against Dengue and Zika
Maternal Antibody-Mediated Enhancement of Dengue Pathogenesis
Maternal Antibody-Mediated Enhancement of Dengue Pathogenesis
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