Transmissible gastroenteritis virus infection induces apoptosis through FasL- and mitochondria-mediated pathways

Abstract

Transmissible gastroenteritis virus (TGEV) has been reported to induce apoptosis in swine testis (ST) cells. However, the mechanisms underlying TGEV-induced apoptosis are still unclear. In this study we observed that TGEV infection induced apoptosis in porcine kidney (PK-15) cells in a time- and dose-dependent manner. TGEV infection up-regulated FasL, activated FasL-mediated apoptotic pathway, leading to activation of caspase-8 and cleavage of Bid. In addition, TGEV infection down-regulated Bcl-2, up-regulated Bax expression, promoted translocation of Bax to mitochondria, activated mitochondria-mediated apoptotic pathway, which in turn caused the release of cytochrome c and the activation of caspase-9. Both extrinsic and intrinsic pathways activated downstream effector caspase-3, followed by the cleavage of PARP, resulting in cell apoptosis. Moreover, TGEV infection did not induce significant DNA fragmentation in ammonium chloride (NH(4)Cl) pretreated PK-15 cells or cells infected with UV-inactivated TGEV. In turn, block of caspases activation also did not affect TGEV replication. Taken together, this study demonstrates that TGEV-induced apoptosis is dependent on viral replication in PK-15 cells and occurs through activation of FasL- and mitochondria-mediated apoptotic pathways.

<i>In vitro</i> Anti-Gastric Tumor Activities and Possible Mechanisms of Action of Paederosidic Acid from <i>Paederia scandens</i> (Lour) Merrill

“…Caspase proteins play pivotal roles in initiation and execution of apoptosis. Caspase-3 is one of the effectors in initiation of apoptosis and caspase-3 can be commonly activated by caspase-9 [12,13]. The B-cell lymphoma/leukemia-2(Bcl-2) family can significantly regulate apoptosis as an activator or as an inhibitor.…”

“…The identification of PA (Fig 1) was accomplished by spectroscopic methods (MS, 1 H NMR and 13 C NMR) and the spectral data of PA are corresponding to literature values [8,10]. PA was purified with purity not less than 98 % (HPLC assay).…”

Inhibitory effect of silver nanomaterials on transmissible virus-induced host cell infections

“…3A), implying the destruction of mitochondria integrity in TGEV-infected ST cells. Moreover, Bcl-2/ Bax ratio is considered as a predictive marker in mitochondriamediated apoptotic pathway [18,21,36]. The pro-apoptotic protein Bax induce the permeabilization of mitochondrial membrane, allowing proteins in the mitochondrial intermembrane space, such as cytochrome C, to escape into the cytosol where they can induce caspase activation and cell apoptosis [37].…”

“…Furthermore, it has been documented that apoptosis is related to the activation and cleavage of the precursor caspase-3, which plays a critical role in maintaining the apoptotic signal induced by various stimulus [21,26]. Importantly, caspases-3 has been considered as a critical mediator of mitochondrial events of apoptosis [42].…”

Extrinsic and Intrinsic Apoptosis Signal Pathway Review

“…For example, transmissible gastroenteritis virus infection can up-regulate the FasL; Subsequently, the Bid protein can be cleaved and cytochrome c release; in the end, Caspase-8 can be activated and the host cell happen apoptosis. [31] Through this way, the pathogens, especially the obligate intracellular parasites, will lost the suitable environment for their life and will die, however, the host will survival and suffer lowest bad effect.…”