INDUCTION OF PROGRAMMED CELL-DEATH (APOPTOSIS) BY INFLUENZA-VIRUS INFECTION IN TISSUE-CULTURE CELLS

The process of cell death caused by influenza virus infection in cultu red MDCK and HeLa cells was analysed. This infection gave rise to nucl ear fragmentation and chromatin condensation accompanied by chromosoma l DNA fragmentation into oligonucleosomes. Chromosomal DNA fragmentati on progressed concomitantly with cell lysis of MDCK cells and HeLa cel ls, producing high and low yields of virus particles, respectively, in dicating that the extent of cell lysis was not proportional to the vir us production. The endonuclease inhibitor zinc blocked DNA fragmentati on in MDCK cells. Cycloheximide inhibited DNA fragmentation as well as cell lysis. Inhibition occurred when the drug was added to the medium within 2 h after infection but not efficiently at 4 h or later. Infec tion induced the Fas Ag gene, which encodes a possible apoptosis-media ting molecule, in the early infectious stage followed by the expressio n of Fas Ag on the cell surface. These results suggested that influenz a virus infection causes apoptotic death of cultured cells, and their fate might be determined at an early stage of the infection by inducti on of an apoptotic gene.