Elucidating mechanisms of interferon gamma that protect against Ebola virus infection

摘要 丝状病毒暴发/流行是零星发生的，但频率和强度都在增加。 由于目前没有批准的丝状病毒疗法，最近的埃博拉病毒（EBOV）爆发 强调需要针对这种高致病性病毒家族的有效治疗。一 对EBOV的有效早期免疫应答的更好的机制理解将确定 用于控制这种感染和相关疾病的潜在免疫学方法。 干扰素γ（IFN-γ）促进控制病毒复制的抗病毒蛋白的产生 并刺激和激活细胞免疫应答。在最近的一系列研究中，我们 表明IFN-γ深刻地抑制巨噬细胞的EBOV感染，这是一个重要的早期 病毒的细胞目标我们还表明IFN-γ保护小鼠免受EBOV攻击， 当小鼠在感染前或感染后24小时被处理时。这些发现提供了证据， IFN-γ刺激后引发的免疫应答有效地控制了EBOV感染， 疾病在这里，我们将探讨先天免疫和细胞免疫对IFN-γ的贡献。 中介保护。总的来说，这里提出的研究将提供关键的机制见解， 这种免疫途径控制丝状病毒感染的功效。

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.