H5N1 avian influenza virus induces apoptotic cell death in mammalian airway epit

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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

http://www.ncbi.nlm.nih.gov/pubmed/18787012