Functional tumor necrosis factor-related apoptosis-inducing ligand production by avian influenza virus-infected macrophages.
Severe human disease associated with influenza A H5N1 virus was first detected in Hong Kong in 1997. Its recent reemergence in Asia and high associated mortality highlight the need to understand its pathogenesis. We investigated the roles of death receptor ligands (DRLs) in H5N1 infection. Significant up-regulation of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and TNF-alpha, but not Fas ligand (FasL) mRNA, was detected in human monocyte-derived macrophages (MDMs) infected with avian influenza viruses A/Hong Kong/483/97 (H5N1/97) or its precursor, A/Quail/Hong Kong/G1/97. H5N1/97-infected MDMs exhibited the strongest induction of apoptosis in Jurkat T cells, and it could be reduced by TRAIL-receptor 2 blocking antibody. Furthermore, influenza virus infection enhanced the sensitivity of Jurkat T cells to apoptosis induced by TNF-alpha, TRAIL, and FasL. Our data suggested that functional TRAIL produced by influenza virus-infected MDMs was related to their cytotoxicity and that the enhanced sensitization to DRL-induced apoptosis detected in avian influenza may contribute to disease pathogenesis.
Zhou
Jianfang
J
Department 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.
Law
Helen K W
HK
Cheung
Chung Yan
CY
Ng
Iris H Y
IH
Peiris
J S Malik
JS
Lau
Yu Lung
YL
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D053222:Fas Ligand Protein; D015870:Gene Expression; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D019169:Jurkat Cells; D008264:Macrophages / Q000821:virology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000166:cytology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000096:biosynthesis / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases