Alpha/Beta Interferons Potentiate Virus-Induced Apoptosis through Activation of the FADD/Caspase-8 Death Signaling Pathway

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

“…This suggests that apoptosis induced by the influenza infection mainly depends on the activity of caspase-8. 49 The present study demonstrated that caspase-8 activity in the lungs of animals pretreated with Ad.HO-1 was similar to that of naive animals, which was associated with increased survival. In contrast, Ad.HO-1 overexpression did not affect caspase-3 activity, suggesting that modulation of caspase-8 activity is essential in protecting cells infected with influenza virus.…”

Avian Influenza Virus A/HK/483/97(H5N1) NS1 Protein Induces Apoptosis in Human Airway Epithelial Cells

“…This event leads to the recruitment and activation of an adapter protein, FADD (Fas-associated death domain-containing protein), resulting in the activation of caspases that exist as inactive zymogens in normal cells (8,39). The apical target of FADD is caspase-8/FLICE (2,32). Activated caspase-8 is able to cleave additional downstream caspases, including caspase-3, that mediate apoptosis.…”

Host defense, viruses and apoptosis

“…A slightly different model favored by ourselves, proposes that IFN can establish an antiviral state that can result in either cell death or cell survival, depending on the stimulus, such as type of virus. 55 This may explain why IFN is able to actually sensitize certain cells to influenza virus or dsRNA-mediated apoptosis but protect against VSV replication. 55 Evidence indicates that IFN is able to inhibit virus replication and virus-induced apoptosis by mechanisms that likely involves the early blocking of viral transcription/translation as well as genome replication which could activate stress-related cell death (see below).…”

“…53 ± 57 The mechanism by which IFN appears to sensitize cells to apoptosis appears to be predominantly via the FADD/ caspase-8 signaling, since IFN-induced cell death could be prevented by inhibitors of caspase-8, by dominant-negative variants of FADD or in cells lacking FADD, but not those lacking Apaf-1. 55,56 Although the pathways governing IFNinduced apoptosis remain to be unraveled it is possible that as yet uncharacterized IFN-induced proteins may govern the regulation of death induced signaling complexes (DISCs) that comprise FADD/caspase-8. 55 Currently, one model of IFN-induced antiviral action suggests that only a virus infected cell producing IFN, is likely to undergo apoptosis.…”

“…55,56 Although the pathways governing IFNinduced apoptosis remain to be unraveled it is possible that as yet uncharacterized IFN-induced proteins may govern the regulation of death induced signaling complexes (DISCs) that comprise FADD/caspase-8. 55 Currently, one model of IFN-induced antiviral action suggests that only a virus infected cell producing IFN, is likely to undergo apoptosis. 57 In this model, IFN is able to function in an autocrine manner to induce the death of the infected cell.…”