Induction of programmed cell death (apoptosis) by influenza virus infection in tissue culture cells

Abstract

The process of cell death caused by influenza virus infection in cultured MDCK and HeLa cells was analysed. This infection gave rise to nuclear fragmentation and chromatin condensation accompanied by chromosomal DNA fragmentation into oligonucleosomes. Chromosomal DNA fragmentation progressed concomitantly with cell lysis of MDCK cells and HeLa cells, producing high and low yields of virus particles, respectively, indicating that the extent of cell lysis was not proportional to the virus production. The endonuclease inhibitor zinc blocked DNA fragmentation 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. Infection induced the Fas Ag gene, which encodes a possible apoptosismediating molecule, in the early infectious stage followed by the expression of Fas Ag on the cell surface. These results suggested that influenza virus infection causes apoptotic death of cultured cells, and their fate might be determined at an early stage of the infection by induction of an apoptotic gene.

Adenovirus-mediated transfer of heme oxygenase-1 cDNA attenuates severe lung injury induced by the influenza virus in mice

“…31,42,43 Consistent with previous findings that influenza virus inoculation results in severe apoptosis of respiratory epithelium, inoculation with H1N1 in our study resulted in a marked increase in the number of respiratory epithelial cells and inflammatory cells with damaged DNA. [44][45][46] In contrast, animals receiving pretreatment of Ad.HO-1 demonstrated marked reduction in cells positive for DNA damage, thus preventing injury.…”

Caspase 8-dependent sensitization of cancer cells to TRAIL-induced apoptosis following reovirus-infection

“…Previous studies have suggested that other members of the TNFR death receptor superfamily may also be involved in virus-induced apoptosis. Alteration of the cell surface expression of Fas may be involved in virus-induced, or viral regulation of, apoptosis in cells infected with in¯uenza virus (Takizawa et al, 1993(Takizawa et al, , 1995, herpes simplex virus type 2 (Sieg et al, 1996), bovine herpesvirus 4 (BHV 4) (Wang et al, 1997), adenovirus (Tollefson et al, 1998) and human immunode®ciency virus type 1 (HIV 1) (Conaldi et al, 1998;Kaplan and Sieg, 1998). Similarly, apoptosis induced by Hepatitis B (Su and Schneider, 1997), HIV-1 (Herbein et al, 1998), BHV 4 (Wang et al, 1997) parvovirus H-1 (Rayet et al, 1998) and Theiler's murine encephalomyelitis virus (Jelachich and Lipton, 2001), may involve the TNFR signaling pathway.…”

Host cell manipulation by the human pathogen Toxoplasma gondii

“…Induction of apoptosis (also known programmed cell death) is a common host response to infection with a variety of viruses, bacteria, and eukaryotic pathogens [83,84]. In this manner, infected organisms reduce the replication and the spread of pathogens.…”