Peng J, Ran Y, Xie H, Deng L, Li C, Ling C. Sarco/Endoplasmic Reticulum Ca 2+ Transporting ATPase (SERCA) Modulates Autophagic, Inflammatory, and Mitochondrial Responses during Influenza A Virus Infection in Human Lung Cells. J Virol. 2021 Mar 10:JVI.00217-21
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.
See Also:
Latest articles in those days:
- Highly pathogenic avian influenza A(H5N1) virus in a common bottlenose dolphin (Tursiops truncatus) in Florida 4 hours ago
- Evidence of Reverse Zoonotic Transmission of Human Seasonal Influenza A Virus (H1N1, H3N2) Among Cats 4 hours ago
- Evolution and Antigenic Differentiation of Avian Influenza A(H7N9) Virus, China 4 hours ago
- Evolution of H7N9 highly pathogenic avian influenza virus in the context of vaccination 1 days ago
- Cost-effectiveness of high-dose influenza vaccination in the Netherlands: Incorporating the impact on both respiratory and cardiovascular hospitalizations 1 days ago
[Go Top] [Close Window]