Knockdown of specific host factors protects against influenza virus-induced cell death

A T Tran1, M N Rahim, C Ranadheera

  • 1Manitoba Centre for Proteomics and Systems Biology, Winnipeg, Manitoba R3E 3P4, Canada.

Cell Death & Disease
|August 17, 2013
PubMed

Insights

Researchers identified host genes crucial for influenza virus-induced cell death. Silencing genes like USP47 and TNFSF12-TNFSF13 (TWE-PRIL) protected cells, revealing new targets for antiviral strategies against influenza infection.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Influenza virus infection frequently causes cell death, a process implicated in viral replication.
  • Host-mediated cell death pathways, including those involving NF-κB, play a complex role in influenza pathogenesis.
  • Limited understanding exists regarding the specific host cell death pathways governing influenza-induced cytopathology and replication.

Purpose of the Study:

  • To identify host genes essential for influenza virus-induced cell death.
  • To discover host factors that, when silenced, confer resistance to influenza-induced cell death.
  • To explore novel therapeutic targets for controlling influenza virus replication.

Main Methods:

  • Genome-wide lentiviral-mediated human gene silencing in A549 cells.
  • High-throughput screening to identify genes whose silencing confers resistance to influenza-induced cell death.
  • Independent validation of candidate genes using small interfering RNA (siRNA) and multiple shRNA clones.

Main Results:

  • Identification of 138 host genes required for influenza-induced cell death in reproducible screens.
  • Silencing of 19 specific genes conferred >85% protection against influenza-induced cell death.
  • USP47 knockdown inhibited viral entry, while TNFSF13 (APRIL) and TNFSF12-TNFSF13 (TWE-PRIL) knockdown impaired late-stage viral replication.

Conclusions:

  • This study successfully identified numerous host genes involved in influenza-induced cell death pathways.
  • USP47, TNFSF13, and TNFSF12-TNFSF13 are critical host factors for influenza virus replication and survival.
  • The findings provide a foundation for understanding viral cytopathology and developing new antiviral therapies targeting host-virus interactions.

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