Influenza A virus infection of mice induces nuclear accumulation of the tumorsuppressor protein p53 in the lung.
To investigate whether the tumor suppressor p53 protein, an indicator of DNA damage and cell stress, accumulates in the course of influenza-virus-induced murine pneumonia at the site of inflammation, female BALB/c mice were infected each with 5 x 10(4) infectious units of influenza virus A, strain Puerto Rico (PR) 8, by instillation into the nose and the pharynx. Two days later the mice became sick. Three and 6 days after infection the lungs of sacrificed infected and uninfected mice were examined. We assessed the presence and localisation of inflammation, the expression of influenza viral and p53 protein, as well as of the WAF1/Cip1/SDI gene product p21. Further, the appearance of nitrotyrosine, as an indicator of the formation of peroxynitrite, and eventually of apoptotic cells was examined. No significant nuclear p53 accumulation was found in influenza virus-infected murine cells in vitro. The results show, that in the course of influenza A virus-mediated murine pneumonia inflammatory bystander cells may cause activation of the tumor suppressor protein p53, due to oxidative stress and DNA damage, with ensuing p53-dependent upregulation of p21. Apoptosis is then mainly due to these indirect processes, with possible involvement of p53.
Technau-Ihling
K
K
Institut für Pathologie, Institut für Medizinische Mikrobiologie und Hygiene der Universität, Freiburg, Germany.
Ihling
C
C
Kromeier
J
J
Brandner
G
G
D000818:Animals; D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology; D002477:Cells; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D005260:Female; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D009980:Influenza A virus / Q000472:pathogenicity*; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; C002744:3-nitrotyrosine; D014443:Tyrosine