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Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells
Published on: June 3, 2012
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Tankyrases positively regulate influenza A virus replication via type I interferon response
Gayan Bamunuarachchi1,2, Kishore Vaddadi1,2, Yurong Liang1,2
1Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, Oklahoma, USA.
Journal of Virology
|October 2, 2025
Summary
Tankyrase 1 and 2 (TNKS1/2) are host factors that promote influenza A virus (IAV) replication. Knocking out TNKS1/2 in cells and mice reduces viral load and increases survival, highlighting them as potential antiviral targets.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Influenza A virus (IAV) poses a significant threat due to drug resistance and pandemic potential.
- Current antivirals target viral proteins, but host-targeting strategies are emerging.
- Poly (ADP-ribose) polymerases (PARPs) are host factors involved in cellular processes, with unclear roles in IAV infection.
Purpose of the Study:
- To screen all 17 PARP members for their role in IAV replication.
- To identify host factors that can be targeted for novel antiviral therapies against IAV.
- To investigate the mechanism by which identified PARPs affect IAV infection.
Main Methods:
- CRISPR activation screening of 17 PARP members in lung epithelial A549 cells.
- CRISPR-Cas9 gene knockout of Tankyrase 1 and 2 (TNKS1/2) in HEK293T cells.
- Assessment of viral replication markers (mRNA, protein, viral titers) in vitro.
- Analysis of host signaling pathways (JNK/c-Jun, Stat) and type I interferon response.
- In vivo studies using Tnks1/2 knockout mice challenged with IAV.
Main Results:
- Tankyrase 1 and 2 (TNKS1/2) were identified as potent proviral factors for IAV.
- TNKS1/2 knockout significantly reduced viral replication and titers in vitro, with double knockout showing a greater effect.
- TNKS1/2 knockout enhanced type I interferon response and activated JNK/c-Jun and Stat signaling pathways.
- Tnks1/2 knockout mice exhibited reduced viral load, increased type I interferon response, and significantly higher survival rates after IAV challenge.
Conclusions:
- TNKS1 and TNKS2 are crucial host factors that promote influenza A virus replication.
- Targeting TNKS1/2 enhances the host's type I interferon response, leading to reduced viral load and increased survival.
- TNKS1/2 represent promising therapeutic targets for developing novel anti-influenza A virus strategies.
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