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Journal Articles American Journal of Physiology - Lung Cellular and Molecular Physiology Year : 2016

Targeting host calpain proteases decreases influenza A virus infection

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Abstract

Influenza A viruses (IAV) trigger contagious acute respiratory diseases. A better understanding of the molecular mechanisms of IAV pathogenesis and host immune responses is required for the development of more efficient treatments of severe influenza. Calpains are intracellular proteases that participate in diverse cellular responses, including inflammation. Here, we used in vitro and in vivo approaches to investigate the role of calpain signaling in IAV pathogenesis. Calpain expression and activity were found altered in IAV-infected bronchial epithelial cells. With the use of small-interfering RNA (siRNA) gene silencing, specific synthetic inhibitors of calpains, and mice overexpressing calpastatin, we found that calpain inhibition dampens IAV replication and IAV-triggered secretion of proinflammatory mediators and leukocyte infiltration. Remarkably, calpain inhibition has a protective impact in IAV infection, since it significantly reduced mortality of mice challenged not only by seasonal H3N2-but also by hypervirulent H5N1 IAV strains. Hence, our study suggests that calpains are promising therapeutic targets for treating IAV acute pneumonia.

Dates and versions

hal-03182699 , version 1 (26-03-2021)

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Fany Blanc, Laetitia Furio, Dorothée Moisy, Hui-Ling Yen, Michel Chignard, et al.. Targeting host calpain proteases decreases influenza A virus infection. American Journal of Physiology - Lung Cellular and Molecular Physiology, 2016, 310 (7), pp.L689-L699. ⟨10.1152/ajplung.00314.2015⟩. ⟨hal-03182699⟩
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