Drugs to cure avian influenza infection – multiple ways to prevent cell death

Yuan, S

Nevertheless, CsA-treated cells are not protected from Bax (B-cell lymphoma 2 (Bcl-2)-associated X protein) or tumor necrosis factor-a (TNFa)-induced mitochondrial dysfunction and cell death. 18 Although H5N1 and H1N1 viruses dramatically induced the TNFa factor in alveolar macrophages, [25] [26] [27] TNF activates both an apoptotic pathway (i.e., TRADD, RIP and JNK) and a survival pathway mediated by NF-kB transcription of survival genes. ROS accumulation triggers a signal to facilitate the TNFa apoptotic pathway. 28 Balance between the pro-apoptotic factor Bax and the anti-apoptotic members of the Bcl-2 family is regulated by the cellular redox status. A tilt in favor of the superoxide abets cell survival and proliferation. On the contrary, a tilt towards hydrogen peroxide generates an intracellular milieu permissive of death execution. 29 Thereby, a high dose of VC as an antioxidant (mainly scavenging hydrogen peroxide) may block both TNF-and Bax-induced apoptosis (Figure 3 ). Rapamycin regulates Bcl-2 and TNFa levels too, but it may exacerbate the H5N1-induced autophagy, which may lead to more severe cell death. 30 Thus, Rapamycin may not be suitable for the treatment of AIV infection.