The PA-interacting host protein nucleolin acts as an antiviral factor during highly pathogenic H5N1 avian influenza
Zhao Gao1,2,3, Jiao Hu1,2,3, Xiaoquan Wang1,2,3
1Animal Infectious Disease Laboratory, School of Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu, China.
Abstract:
Polymerase acidic (PA) protein is a multifunctional regulator of influenza A virus (IAV) replication and pathogenesis. In a previous study, we reported that nucleolin (NCL) is a novel PA-interacting host protein. In this study, we further explored the role of NCL during highly pathogenic H5N1 avian influenza virus infection. We found that depletion of endogenous NCL in mammalian cells by siRNA targeting during H5N1 infection resulted in significantly increased viral polymerase activity, elevated viral mRNA, cRNA and vRNA synthesis, accelerated viral replication, and enhanced apoptosis and necrosis. Moreover, siRNA silencing of NCL significantly exacerbated the inflammatory response, resulting in increased secretion of IL-6, TNF-α, TNF-β, CCL-4, CCL-8, IFN-α, IFN-β and IFN-γ. Conversely, overexpression of NCL significantly decreased IAV replication. Collectively, these data show that NCL acts as a novel potential antiviral factor during H5N1 infection. Further studies exploring the antiviral mechanisms of NCL may accelerate the development of new anti-influenza drugs.
Insights
Nucleolin (NCL) acts as an antiviral factor against H5N1 avian influenza virus. Depleting NCL increases viral replication and inflammation, while its overexpression reduces it, suggesting NCL as a drug target.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Influenza A virus (IAV) polymerase acidic (PA) protein regulates viral replication.
- Nucleolin (NCL) was previously identified as a host protein interacting with PA.
- The role of NCL in highly pathogenic H5N1 avian influenza virus infection requires further investigation.
Purpose of the Study:
- To investigate the role of Nucleolin (NCL) in H5N1 avian influenza virus infection.
- To determine the effect of NCL depletion or overexpression on viral replication and host response.
Main Methods:
- Utilized siRNA to deplete endogenous NCL in mammalian cells during H5N1 infection.
- Quantified viral polymerase activity, viral RNA synthesis (mRNA, cRNA, vRNA), and viral replication.
- Assessed apoptosis, necrosis, and inflammatory cytokine secretion (IL-6, TNF-α, etc.).
- Overexpressed NCL to observe its effect on IAV replication.
Main Results:
- NCL depletion significantly increased viral polymerase activity, RNA synthesis, and replication.
- Silencing NCL enhanced apoptosis, necrosis, and exacerbated inflammatory responses.
- Overexpression of NCL significantly decreased IAV replication.
- NCL demonstrated a significant antiviral effect against H5N1 infection.
Conclusions:
- Nucleolin (NCL) functions as a novel antiviral factor against H5N1 avian influenza virus.
- NCL plays a protective role by inhibiting viral replication and modulating host immune responses.
- Targeting NCL could be a potential therapeutic strategy for developing new anti-influenza drugs.
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