Elucidating mechanisms of interferon gamma that protect against Ebola virus infection

阐明干扰素γ预防埃博拉病毒感染的机制

基本信息

批准号：
10696250
负责人：
Wendy Jean Maury
金额：
$ 19.31万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-02 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10696250
关键词：
Animal Model Antiviral Agents B-Lymphocytes CD8-Positive T-Lymphocytes Cells Cellular Immunity Clinical Research Developing Countries Development Disease Disease Outbreaks Dose Ebola Hemorrhagic Fever Ebola virus Epidemic FDA approved Family Filoviridae Infections Filovirus Frequencies Future Genes Goals Hour IFNGR1 gene Immune Immune response Immunity Immunologics In Vitro Infection Infection Control Innate Immune Response Innate Immune System Interferon Type I Interferon Type II Interferons Investigation Knowledge Macrophage Mediating Mus Natural Immunity Pathogenesis Pathogenicity Pathway interactions Peritoneal Peritoneal Macrophages Peritoneum Pharmaceutical Preparations Phenotype Population Production Property Role Series Severities T-Lymphocyte Testing Therapeutic Tissues Vaccines Viral Viral Pathogenesis Viral Proteins Viral load measurement Viremia Virus Virus Diseases Virus Replication Zaire Ebola virus adaptive immune response cellular targeting combat conditional knockout cost effective effective therapy in vivo insight mouse model pathogenic virus peripheral blood prevent recruit response side effect treatment response

项目摘要

Abstract Filovirus outbreaks/epidemics occur sporadically, but with increasing frequency and intensity. With no current approved filovirus therapeutics, the recent Ebola virus (EBOV) outbreaks emphasize the need for effective treatments against this highly pathogenic family of viruses. A better mechanistic understanding of effective early immune responses to EBOV will identify potential immunological approaches for controlling this infection and associated disease. Interferon gamma (IFN-γ) elicits production of antiviral proteins that control of virus replication and stimulates and activates cellular immune responses. In a series of recent studies, we demonstrated that IFN-γ profoundly inhibits EBOV infection of macrophages, an important early cellular target for the virus. We also showed that IFN-γ protects mice from EBOV challenge when mice were treated 24 hours prior to or after infection. These findings provide evidence that the immune responses elicited following IFN-γ stimulation effectively control EBOV infection and disease. Here, we will explore the contribution of both innate and cellular immunity to IFN-γ- mediated protection. In total, studies proposed here will provide critical mechanistic insights into the efficacy of this immune pathway to control filovirus infections.

抽象的丝状病毒暴发/流行病偶发地发生，但频率和强度的增加。由于没有当前批准的FILOVIRUS疗法，最近的埃博拉病毒（EBOV）暴发强调需要有效治疗这种高度致病的病毒家族。一个对有效的早期免疫反应的更好的机械理解将确定控制这种感染和相关疾病的潜在免疫学方法。干扰素伽马（IFN-γ）引起控制病毒复制的抗病毒蛋白的产生并刺激并激活细胞免疫复杂。在一系列最近的研究中，我们证明IFN-γ深刻抑制了巨噬细胞的EBOV感染，这是一个重要的早期病毒的细胞靶标。我们还表明，IFN-γ可以保护小鼠免受EBOV挑战当小鼠在感染前24小时接受治疗时。这些发现提供了证据表明以下IFN-γ刺激引起的免疫反应有效控制EBOV感染和疾病。在这里，我们将探讨先天和细胞免疫对IFN-γ-的贡献介导的保护。总的来说，这里提出的研究将提供关键的机械洞察力这种免疫途径控制丝状病毒感染的效率。