1. Academic Validation
  2. Sarco/Endoplasmic Reticulum Ca2+ Transporting ATPase (SERCA) Modulates Autophagic, Inflammatory, and Mitochondrial Responses during Influenza A Virus Infection in Human Lung Cells

Sarco/Endoplasmic Reticulum Ca2+ Transporting ATPase (SERCA) Modulates Autophagic, Inflammatory, and Mitochondrial Responses during Influenza A Virus Infection in Human Lung Cells

  • J Virol. 2021 Mar 10;95(10):e00217-21. doi: 10.1128/JVI.00217-21.
Jiaojiao Peng 1 Yeqian Ran 1 Haojun Xie 1 Ling Deng 1 Chufang Li 2 Chen Ling 2
Affiliations

Affiliations

  • 1 State Key Lab of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • 2 State Key Lab of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China [email protected] [email protected].
Abstract

Influenza A virus is an important human pathogen causing significant morbidity and mortality. Numerous host factors and cellular responses are dysregulated during influenza A virus Infection. This includes arrest of autophagic flux dependent on the influenza M2 ion channel, but little is known which host factors participate in this autophagic dysfunction. Sarco/endoplasmic reticulum calcium ATPase (SERCA) is known to regulate transport of calcium ions between the cytoplasm and the sarco/endoplasmic reticulum, and has been positively correlated with autophagic flux. Herein, we found that SERCA activity was suppressed in influenza A virus infected human lung cells (H1395) and that CDN1163, an activator of SERCA, restored autophagic flux and thus reduced autophagosome accumulation caused by the influenza A virus. Activating SERCA activity with CDN1163 also decreased expression of inflammatory cytokines and chemokines and attenuated mitochondrial dysfunction in IAV-infected H1395 cells. Conversely, SERCA inhibition or genetic ablation aggravated the Autophagy dysfunction, mitochondria, and inflammatory responses in the cells infected with influenza A virus. Further study showed that SERCA might regulate the inflammatory response by modulating phosphorylation of MAPK-JNK pathway. These findings showed that the influenza A virus induced autophagic flux blocking, inflammatory response and mitochondrial dysfunction by inhibiting SERCA activity. This study provides further understanding of the host-viral interactions between the Influenza Virus, SERCA activity, Autophagy, inflammatory response, and mitochondrial function. SERCA may be a potential host target for decreasing inflammatory and superoxide injury during influenza A virus Infection.IMPORTANCE:IAV is a major cause of infectious respiratory diseases, characterized by a marked respiratory tract inflammatory response that causes morbidity and mortality in seasonal epidemics, or pandemic outbreaks. SERCA is a critical component in maintaining cellular calcium levels, and is positively correlated with autophagic flux. Here, we discovered that SERCA is suppressed in IAV-infected human lung cells and influenza A virus induces blocking of autophagic flux, inflammatory response and mitochondrial dysfunction by inhibiting SERCA. We posit that the pharmacological activation of SERCA can be a powerful intervention strategy to prevent Autophagy arrest, inflammatory response, and mitochondrial dysfunction in IAV-infected cells. Therefore, SERCA activity modulation could be a potential therapeutic strategy for managing clinical symptoms of severe influenza disease.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-101455
    99.86%, SERCA Activator