AML1 protein interacts with influenza A virus neuraminidase and upregulates IFN-β response in infected mammalian cells.
AML1 蛋白与甲型流感病毒神经氨酸酶相互作用，在感染的哺乳动物细胞中上调IFN-β 应答。
- 作者列表："Gaur P","Kumar P","Sharma A","Lal SK
: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) 的一种完整膜蛋白，主要辅助子代病毒粒子的释放，遵循细胞内病毒复制周期。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 (AML 1) 是IAV-NA的新型相互作用伴侣。通过IAV感染细胞中的免疫共沉淀和体外偶联转录/翻译系统进一步验证了这种相互作用。有趣的是，我们发现IAV感染时AML1 的表达增加，且呈剂量依赖性。正如预期的那样，我们还观察到IFN-β 水平的增加，这是抵御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感染时被诱导，并导致IFN-β 的诱导。因此，AML1 被认为是IFN诱导的重要参与者，并在针对IAV感染的抗病毒反应中发挥作用。研究的意义和影响: 流感流行和大流行是对人类健康的持续威胁。抗病毒治疗的发展集中在重要和主要的IAV蛋白作为靶点。然而，这种病毒变异的速度使得这项任务具有挑战性。因此，下一代方法的目标是帮助病毒复制的宿主细胞蛋白。本研究报道了一种新的宿主-病毒相互作用，即急性髓系白血病标志物 1 (AML 1) 与甲型流感神经氨酸酶 (IAV-NA)。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对感染细胞中的这种新的先天防御途径有更多的了解。
METHODS::Since mid-December of 2019, coronavirus disease 2019 (COVID-19) infection has been spreading from Wuhan, China. The confirmed COVID-19 patients in South Korea are those who came from or visited China. As secondary transmissions have occurred and the speed of transmission is accelerating, there are rising concerns about community infections. The 54-year old male is the third patient diagnosed with COVID-19 infection in Korea. He is a worker for a clothing business and had mild respiratory symptoms and intermittent fever in the beginning of hospitalization, and pneumonia symptoms on chest computerized tomography scan on day 6 of admission. This patient caused one case of secondary transmission and three cases of tertiary transmission. Hereby, we report the clinical findings of the index patient who was the first to cause tertiary transmission outside China. Interestingly, after lopinavir/ritonavir (Kaletra, AbbVie) was administered, β-coronavirus viral loads significantly decreased and no or little coronavirus titers were observed.
METHODS::In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.
METHODS::There is a current worldwide outbreak of a new type of coronavirus (2019-nCoV), which originated from Wuhan in China and has now spread to 17 other countries. Governments are under increased pressure to stop the outbreak spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak sites and from laboratories supporting the investigation. This paper aggregates and consolidates the virology, epidemiology, clinical management strategies from both English and Chinese literature, official news channels, and other official government documents. In addition, by fitting the number of infections with a single-term exponential model, we report that the infection is spreading at an exponential rate, with a doubling period of 1.8 days.