hnRNPAB inhibits Influenza A virus infection by disturbing polymerase activity

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Influenza A virus (IAV) poses a significant global health threat, necessitating novel antiviral strategies.
• IAV RNA-dependent RNA polymerase (FluPol) is crucial for viral transcription and replication, making it a key target for drug development.

Purpose of the Study:

• To identify host factors that inhibit IAV replication.
• To elucidate the mechanism by which hnRNPAB exerts its anti-influenza activity.

Main Methods:

• Identification of host factors interacting with IAV proteins.
• Biochemical assays to study protein-protein interactions (hnRNPAB, NP, PB1).
• In vivo studies using hnRNPAB-deficient mice to assess influenza infection outcomes.

Main Results:

• Heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB) was identified as an anti-influenza host factor.
• hnRNPAB interacts with the IAV nucleoprotein (NP) and inhibits the PB1-NP interaction via a specific C-terminal peptide (aa 318-322).
• hnRNPAB deficiency in mice led to increased viral loads, heightened cytokine responses, and higher mortality following IAV infection.

Conclusions:

• hnRNPAB disrupts the influenza virus polymerase complex conformation, thereby inhibiting viral infection.
• This study reveals hnRNPAB as a critical component of the host's anti-influenza defense.
• Targeting the hnRNPAB-FluPol interaction presents a promising avenue for developing new antiviral therapeutics.