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Functional tumor necrosis factor-related apoptosis-inducing ligand production by avian influenza virus-infected

Jianfang Zhou1, Helen K W Law, Chung Yan Cheung

  • 1Department of Paediatrics and Adolescent Medicine, Hong Kong Jockey Club Clinical Research Centre, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.

The Journal of Infectious Diseases
|March 7, 2006
PubMed

Insights

Avian influenza H5N1 infection up-regulates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This functional TRAIL contributes to H5N1 pathogenesis by increasing cytotoxicity and apoptosis in immune cells.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Severe human disease linked to avian influenza A H5N1 virus first emerged in Hong Kong in 1997.
  • Recent H5N1 outbreaks in Asia underscore the critical need to understand its disease mechanisms.

Purpose of the Study:

  • To investigate the role of death receptor ligands (DRLs) in H5N1 virus infection pathogenesis.
  • To determine the impact of H5N1 infection on immune cell apoptosis and cytotoxicity.

Main Methods:

  • Human monocyte-derived macrophages (MDMs) were infected with H5N1/97 and precursor viruses.
  • mRNA levels of DRLs (TRAIL, TNF-alpha, FasL) were quantified.
  • Apoptosis induction in Jurkat T cells by infected MDMs and DRLs was assessed.
  • Blocking antibodies against TRAIL-receptor 2 were used to evaluate TRAIL's role.

Main Results:

  • H5N1 infection significantly upregulated tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and TNF-alpha mRNA in MDMs.
  • H5N1-infected MDMs induced significant apoptosis in Jurkat T cells, which was partially mediated by TRAIL.
  • Influenza virus infection enhanced Jurkat T cell sensitivity to apoptosis induced by TNF-alpha, TRAIL, and FasL.

Conclusions:

  • Functional TRAIL produced by H5N1-infected MDMs contributes to cytotoxicity.
  • Enhanced sensitivity to DRL-induced apoptosis in avian influenza may play a role in disease pathogenesis.

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