ArticlePloS one2011
Influenza A virus nucleoprotein exploits Hsp40 to inhibit PKR activation.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 76 citations in OpenAlex.
- Positive Regulation of Cellular Proteins by Influenza Virus for Productive Infection.International journal of molecular sciences · 2025Review
- Interaction Network Characterization of Infectious Bronchitis Virus Nsp2 with Host Proteins.Veterinary sciences · 2024Article
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- Influenza Virus Host Restriction Factors: The ISGs and Non-ISGs.Pathogens (Basel, Switzerland) · 2024Review
- Interaction of Influenza A Nucleoprotein with Host hnRNP-C Is Implicated in Viral Replication.International journal of molecular sciences · 2022Article
- The Role of Nucleoprotein in Immunity to Human Negative-Stranded RNA Viruses-Not Just Another Brick in the Viral Nucleocapsid.Viruses · 2022Review
- Article
- A Review and Meta-Analysis of Influenza Interactome Studies.Frontiers in microbiology · 2022Review
- Host cell stress response as a predictor of COVID-19 infectivity and disease progression.Frontiers in molecular biosciences · 2022Review
- Recent Progress in Recombinant Influenza Vaccine Development Toward Heterosubtypic Immune Response.Frontiers in immunology · 2022Review
- TRIM28 functions as a negative regulator of aggresome formation.Autophagy · 2021Article
- Review
- Unravelling the Immunomodulatory Effects of Viral Ion Channels, towards the Treatment of Disease.Viruses · 2021Review
- Inhibition of PKR by Viruses.Frontiers in microbiology · 2021Review
- HSC70 Inhibits Spring Viremia of Carp Virus Replication by Inducing MARCH8-Mediated Lysosomal Degradation of G Protein.Frontiers in immunology · 2021Article
- Influenza A Virus: Host-Virus Relationships.Viruses · 2020Article
- Stress proteins: the biological functions in virus infection, present and challenges for target-based antiviral drug development.Signal transduction and targeted therapy · 2020Review
- SARS-CoV-2: At the Crossroad Between Aging and Neurodegeneration.Movement disorders : official journal of the Movement Disorder Society · 2020Article
- Upregulation of miR-101 during Influenza A Virus Infection Abrogates Viral Life Cycle by Targeting mTOR Pathway.Viruses · 2020Article
- Proteostasis in Viral Infection: Unfolding the Complex Virus-Chaperone Interplay.Cold Spring Harbor perspectives in biology · 2020Review
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDouble-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. PKR activity is regulated by a 58 kilo Dalton cellular inhibitor (P58(IPK)), which is present in inactive state as a complex with Hsp40 under normal conditions. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. However the influenza virus component responsible for PKR inhibition through P58(IPK) activation was hitherto unknown. PRINCIPAL
findingsHuman heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. This interaction was confirmed by co-immunoprecipitation studies from mammalian cells transfected with IAV NP expressing plasmid. Further, the IAV NP-Hsp40 interaction was validated in mammalian cells infected with various seasonal and pandemic strains of influenza viruses. Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation. We observed that, plasmid based expression of NP in mammalian cells leads to decrease in PKR phosphorylation. Furthermore, inhibition of NP expression during influenza virus replication led to PKR activation and concomitant increase in eIF2α phosphorylation. Inhibition of NP expression also led to reduced IRF3 phosphorylation, enhanced IFN β production and concomitant reduction of virus replication. Taken together our data suggest that NP is the viral factor responsible for P58(IPK) activation and subsequent inhibition of PKR-mediated host response during IAV infection. SIGNIFICANCE: Our findings demonstrate a novel role of IAV NP in inhibiting PKR-mediated anti-viral host response and help us understand P58(IPK) mediated inhibition of PKR activity during IAV infection.
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