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Arch Virol. 2018 Jul 5. doi: 10.1007/s00705-018-3926-3. [Epub ahead of print]
The PA-interacting host protein nucleolin acts as an antiviral factor during highly pathogenic H5N1 avian influenza virus infection.
Gao Z1,2,3, Hu J1,2,3, Wang X1,2,3, Yang Q1,2,3, Liang Y1,2,3, Ma C1,2,3, Liu D1,2,3, Liu K1,2,3, Hao X1,2,3, Gu M1,2,3, Liu X1,2,3, Jiao XA2,4,3, Liu X5,6,7.
Author information
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.
PMID: 29974255 DOI: 10.1007/s00705-018-3926-3
The PA-interacting host protein nucleolin acts as an antiviral factor during highly pathogenic H5N1 avian influenza virus infection.
Gao Z1,2,3, Hu J1,2,3, Wang X1,2,3, Yang Q1,2,3, Liang Y1,2,3, Ma C1,2,3, Liu D1,2,3, Liu K1,2,3, Hao X1,2,3, Gu M1,2,3, Liu X1,2,3, Jiao XA2,4,3, Liu X5,6,7.
Author information
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.
PMID: 29974255 DOI: 10.1007/s00705-018-3926-3