Differential onset of apoptosis in influenza A virus H5N1- and H1N1-infected human blood macrophages.
Pathogenesis of the highly pathogenic avian influenza virus A/Hong Kong/483/97 (H5N1/97) remains to be investigated. It was demonstrated recently that H5N1 dysregulation of proinflammatory cytokines in human macrophages is a p38-kinase-dependent process. The results indicated that macrophages may play a role in disease severity. To investigate cellular responses to H5N1 infection further, apoptosis and its related pathways were studied in primary blood macrophages. Here, it is shown that the H5N1/97 virus triggered apoptosis, including caspases and PARP activation, in infected macrophages with a delayed onset compared with H1N1 counterparts. Similar results were also found in human macrophages infected by precursors of the H5N1/97 virus. Thus, these results showed that the delay in apoptosis onset in macrophages infected by H5N1/97 and its related precursor subtypes may be a means for the pathogens to have longer survival in the cells; this may contribute to the pathogenesis of H5N1 disease in humans.
Mok
Chris K P
CKP
Immunology Research Laboratory, Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.
Lee
Davy C W
DCW
Immunology Research Laboratory, Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.
Cheung
Chung-Yan
CY
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.
Peiris
Malik
M
Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.
Lau
Allan S Y
ASY
Immunology Research Laboratory, Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000096:biosynthesis; D002478:Cells, Cultured; D024161:Collagen Type XI / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity*; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D007251:Influenza, Human / Q000821:virology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000821:virology*
C499319:COL11A2 protein, human; D024161:Collagen Type XI; D020169:Caspases