School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Department of Biotechnology, Mewar University, Chittorgarh, Rajasthan, India.
Lett Appl Microbiol. 2020 Apr;70(4):252-258. doi: 10.1111/lam.13279. Epub 2020 Feb 17.
Neuraminidase (NA) is an integral membrane protein of influenza A virus (IAV) and primarily aids in the release of progeny virions, following the intracellular viral replication cycle. In an attempt to discover new functions of NA, we conducted a classical yeast two-hybrid screen and found acute myeloid leukaemia marker 1 (AML1) as a novel interacting partner of IAV-NA. The interaction was further validated by co-immunoprecipitation in IAV-infected cells and in an in vitro coupled transcription/translation system. Interestingly, we found an increase in the expression of AML1 upon IAV infection in a dose-dependent manner. As expected, we also observed an increase in the IFN-β levels, the first line of defence against viral infections. Subsequently, when AML1 was downregulated using siRNA, the IFN-β levels were found to be remarkably reduced. Our study also shows that AML1 is induced upon IAV infection and results in the induction of IFN-β. Thus, AML1 is proposed to be an important player in IFN induction and has a role in an antiviral response against IAV infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Influenza epidemics and pandemics are constant threats to human health. Development of antiviral therapeutics has focused on important and major IAV proteins as targets. However, the rate at which this virus mutates makes the task challenging. Thus, next-generation approaches aim at host cellular proteins that aid the virus in its replication. This study reports a new host-virus interaction, of acute myeloid leukaemia marker 1 (AML1) with influenza A neuraminidase (IAV-NA). We have found that this interaction has a direct effect on the upregulation of host IFN-β response. Further studies may lead to a greater understanding of this new innate defence pathway in infected cells.
神经氨酸酶（NA）是甲型流感病毒（IAV）的一种完整的膜蛋白，主要有助于在细胞内病毒复制周期后释放子代病毒粒子。为了发现 NA 的新功能，我们进行了经典的酵母双杂交筛选，发现急性髓系白血病标志物 1（AML1）是 IAV-NA 的一个新的相互作用伙伴。在 IAV 感染的细胞中和体外偶联转录/翻译系统中，通过共免疫沉淀进一步验证了这种相互作用。有趣的是，我们发现 IAV 感染后 AML1 的表达呈剂量依赖性增加。正如预期的那样，我们还观察到 IFN-β水平的增加，IFN-β是对抗病毒感染的第一道防线。随后，当使用 siRNA 下调 AML1 时，发现 IFN-β水平显著降低。我们的研究还表明，AML1 在 IAV 感染后被诱导，导致 IFN-β的诱导。因此，AML1 被提议作为 IFN 诱导的重要参与者，并在抗病毒反应中发挥作用，以对抗 IAV 感染。
流感的流行和大流行一直是人类健康的威胁。抗病毒治疗的开发侧重于作为靶标的 IAV 的重要和主要蛋白。然而，这种病毒的突变速度使得任务具有挑战性。因此，下一代方法针对的是有助于病毒复制的宿主细胞蛋白。本研究报告了急性髓系白血病标志物 1（AML1）与甲型流感神经氨酸酶（IAV-NA）之间的新的宿主-病毒相互作用。我们发现这种相互作用对宿主 IFN-β反应的上调有直接影响。进一步的研究可能会导致对感染细胞中这种新的先天防御途径的更好理解。
