value
| - Abstract Most viruses encode proteins that modulate cell-death signaling by the host. For hepatitis C virus (HCV) infection, apoptosis and other forms of cell-death have been observed in vitro and in vivo but the detailed understanding of this intricate viral-host interplay is unclear. This study examined the role played by the HCV p7 protein in the induction of cell-death. By measuring caspase-3/7 activation and cleavage of endogenous PARP, two hallmarks of apoptosis, the overexpression of p7 protein was shown to induce apoptosis in Huh7.5 cells. Furthermore, p7-induced apoptosis is caspase-dependent and involves both the intrinsic and extrinsic pathways. Similar to the M2 protein of influenza A virus, p7-induced apoptosis is independent of its ion channel activity. Coimmunoprecipitation experiments further showed that both M2 and p7 interact with the essential autophagy protein Beclin-1. However, only the M2 protein could cause an increase in the level of LC3-II, which is an indicator of autophagic activity. Thus, although the p7 protein is functionally similar to the well-characterized M2 protein, they differ in their activation of autophagic cell-death. Taken together, these results shed more light on the relationship between the HCV p7 ion channel protein and cell-death induction in host cells.
|