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 DN A damage and cell stress, accumulates in the course of influenza-virus-indu ced murine pneumonia at the site of inflammation, female BALB/c mice were i nfected each with 5 x 10(4) infectious units of influenza virus A, strain P uerto 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 s acrificed infected and uninfected mice were examined. We assessed the prese nce and localisation of inflammation, the expression of influenza viral and p53 protein, as well as of the WAF1/Cip1/SDI gene product p21. Further, th e appearance of nitrotyrosine, as an indicator of the formation of peroxyni trite, and eventually of apoptotic cells was examined. No significant nucle ar p53 accumulation was found in influenza virus-infected murine cells in v itro. The results show, that in the course of influenza A virus-mediated mu rine pneumonia inflammatory bystander cells may cause activation of the tum or suppressor protein p53, due to oxidative stress and DNA damage, with ens uing p53-dependent upregulation of p21. Apoptosis is then mainly due to the se indirect processes, with possible involvement of p53.