Giuseppe
Emeritus
J Virol. 2008 Sep 11. [Epub ahead of print]
H5N1 avian influenza virus induces apoptotic cell death in mammalian airway epithelial cells.
Daidoji T, Koma T, Du A, Yang CS, Ueda M, Ikuta K, Nakaya T. - International Research Center for Infectious Diseases, and Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
In recent years, the highly pathogenic avian influenza virus H5N1 has raised serious worldwide concern about an influenza pandemic; however, the biology of H5N1 pathogenesis is largely unknown.
To elucidate the mechanism of H5N1 pathogenesis, we prepared primary airway epithelial cells from alveolar tissues from 1-year-old pigs, and measured the growth kinetics of 3 avian H5 influenza viruses (A/Crow/Kyoto/53/2004 [H5N1], A/Duck/Hong Kong/342/78 [H5N2], and A/Duck/Hong Kong/820/80 [H5N3]), the resultant cytopathicity, and possible associated mechanisms.
H5N1, but not the other H5 viruses, strongly induced cell death in porcine alveolar epithelial cells (pAEpC), although all 3 viruses induced similar cytopathicity in chicken embryonic fibroblasts.
Intracellular viral growth and the production of progeny viruses were comparable in pAEpC infected with each H5 virus.
In contrast, TUNEL-positive cells were detected only in H5N1-infected pAEpC, and the activities of caspase 3, 8, and 9 were significantly elevated in pAEpC infected with H5N1, but not with H5N2 and H5N3.
These results suggest that only H5N1 induces apoptosis in pAEpC.
The H5N1 cytopathicity was inhibited by adding the caspase inhibitor z-VAD-FMK; however, there were no significant differences in viral growth or release of progeny viruses.
Further investigations using reverse genetics demonstrated that H5N1-HA protein plays a critical role in inducing caspase-dependent apoptosis in infected pAEpC.
H5N1-specific cytopathicity was also observed in human primary airway epithelial cells.
Taken together, these data suggest that avian H5N1 influenza virus leads to substantial cell death in mammalian airway epithelial cells due to the induction of apoptosis.
PMID: 18787012 [PubMed - as supplied by publisher
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H5N1 avian influenza virus induces apoptotic cell death in mammalian airway epithelial cells.
Daidoji T, Koma T, Du A, Yang CS, Ueda M, Ikuta K, Nakaya T. - International Research Center for Infectious Diseases, and Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.
In recent years, the highly pathogenic avian influenza virus H5N1 has raised serious worldwide concern about an influenza pandemic; however, the biology of H5N1 pathogenesis is largely unknown.
To elucidate the mechanism of H5N1 pathogenesis, we prepared primary airway epithelial cells from alveolar tissues from 1-year-old pigs, and measured the growth kinetics of 3 avian H5 influenza viruses (A/Crow/Kyoto/53/2004 [H5N1], A/Duck/Hong Kong/342/78 [H5N2], and A/Duck/Hong Kong/820/80 [H5N3]), the resultant cytopathicity, and possible associated mechanisms.
H5N1, but not the other H5 viruses, strongly induced cell death in porcine alveolar epithelial cells (pAEpC), although all 3 viruses induced similar cytopathicity in chicken embryonic fibroblasts.
Intracellular viral growth and the production of progeny viruses were comparable in pAEpC infected with each H5 virus.
In contrast, TUNEL-positive cells were detected only in H5N1-infected pAEpC, and the activities of caspase 3, 8, and 9 were significantly elevated in pAEpC infected with H5N1, but not with H5N2 and H5N3.
These results suggest that only H5N1 induces apoptosis in pAEpC.
The H5N1 cytopathicity was inhibited by adding the caspase inhibitor z-VAD-FMK; however, there were no significant differences in viral growth or release of progeny viruses.
Further investigations using reverse genetics demonstrated that H5N1-HA protein plays a critical role in inducing caspase-dependent apoptosis in infected pAEpC.
H5N1-specific cytopathicity was also observed in human primary airway epithelial cells.
Taken together, these data suggest that avian H5N1 influenza virus leads to substantial cell death in mammalian airway epithelial cells due to the induction of apoptosis.
PMID: 18787012 [PubMed - as supplied by publisher
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