Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression.
Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression.
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低氧诱导因子通过调节核仁蛋白的表达抑制呼吸道合胞病毒感染。
DOI：
10.1016/j.isci.2023.108763
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发表时间：
2024-01-19
期刊：
影响因子：
5.8
通讯作者：
McKeating, Jane A.
中科院分区：
文献类型：
--
作者：
Zhuang, Xiaodong;Gallo, Giulia;Sharma, Parul;Ha, Jiyeon;Magri, Andrea;Borrmann, Helene;Harris, James M.;Tsukuda, Senko;Bentley, Eleanor;Kirby, Adam;de Neck, Simon;Yang, Hongbing;Balfe, Peter;Wing, Peter A. C.;Matthews, David;Harris, Adrian L.;Kipar, Anja;Stewart, James P.;Bailey, Dalan;McKeating, Jane A.
关键词：
呼吸道合胞病毒(RSV)是一个全球性的医疗问题，可引起幼儿和老年人的呼吸道疾病。我们对定义感染易感性和疾病严重程度的宿主途径的了解有限。低氧诱导因子(HIF)定义了对低氧的代谢反应，并调节下呼吸道的炎症反应。我们证明了HIF在抑制RSV进入和RNA复制方面的作用。我们发现，低氧和HIF脯氨酸羟基酶抑制剂减少了RSV进入受体核仁素的表达，并抑制了病毒细胞-细胞融合。我们发现了一个受HIF调控的microRNA，miR-494，它调节核仁素的表达。在RSV感染的小鼠中，临床批准的HIF Prolyl-Hylylase抑制剂daprodustat的治疗减少了肺部感染病毒的水平和渗透的单核细胞和中性粒细胞。这项研究强调了HIF信号在限制RSV感染和相关炎症的多个方面的作用，并为这种呼吸道病原体的未来治疗方法提供了信息。HIF限制RSV细胞-细胞融合和复制HIF激活miR-494抑制核仁素表达HIF Pro-羟基酶抑制剂限制RSV感染小鼠HIF抑制下呼吸道单核细胞和中性粒细胞的渗透分子生物学；Omics；转录组学
Respiratory syncytial virus (RSV) is a global healthcare problem, causing respiratory illness in young children and elderly individuals. Our knowledge of the host pathways that define susceptibility to infection and disease severity are limited. Hypoxia inducible factors (HIFs) define metabolic responses to low oxygen and regulate inflammatory responses in the lower respiratory tract. We demonstrate a role for HIFs to suppress RSV entry and RNA replication. We show that hypoxia and HIF prolyl-hydroxylase inhibitors reduce the expression of the RSV entry receptor nucleolin and inhibit viral cell-cell fusion. We identify a HIF regulated microRNA, miR-494, that regulates nucleolin expression. In RSV-infected mice, treatment with the clinically approved HIF prolyl-hydroxylase inhibitor, Daprodustat, reduced the level of infectious virus and infiltrating monocytes and neutrophils in the lung. This study highlights a role for HIF-signalling to limit multiple aspects of RSV infection and associated inflammation and informs future therapeutic approaches for this respiratory pathogen. HIFs limit RSV cell-cell fusion and replication HIFs activate miR-494 which suppresses nucleolin expression HIF prolyl-hydroxylase inhibitor limits RSV infection in mice HIFs suppress infiltrating monocytes and neutrophils in the lower respiratory tract Molecular biology; Omics; Transcriptomics
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RSV感染期间缺氧诱导因子（HIF）-1的氧无氧稳定。
影响因子：
3.7
作者：
Haeberle, Helene A.;Duerrstein, Carin;Rosenberger, Peter;Hosakote, Yashoda M.;Kuhlicke, Johannes;Kempf, Volkhard A. J.;Garofalo, Roberto P.;Eltzschig, Holger K.
通讯作者：
Eltzschig, Holger K.
影响因子：
7.8
作者：
Mastrangelo P;Norris MJ;Duan W;Barrett EG;Moraes TJ;Hegele RG
通讯作者：
Hegele RG
影响因子：
1.9
作者：
Akizawa, Tadao;Otsuka, Tetsuro;Ueno, Mai
通讯作者：
Ueno, Mai
影响因子：
15.9
作者：
Hickey, Michele M.;Richardson, Theresa;Simon, M. Celeste
通讯作者：
Simon, M. Celeste
影响因子：
14.9
作者：
Greasley, PJ;Bonnard, C;Amati, B
通讯作者：
Amati, B