Bax Is Activated during Rotavirus-Induced Apoptosis through the Mitochondrial Pathway

Abstract

Rotaviruses are the leading cause of infantile viral gastroenteritis worldwide. Mature enterocytes of the small intestine infected by rotavirus undergo apoptosis, and their replacement by less differentiated dividing cells probably leads to defective absorptive function of the intestinal epithelium, which, in turn, contributes to osmotic diarrhea and rotavirus pathogenesis. Here we show that infection of MA104 cells by the simian rhesus rotavirus strain RRV induced caspase-3 activation, DNA fragmentation, and cleavage of poly(ADP-ribose) polymerase; all three phenomena are features of apoptosis. RRV induced the release of cytochrome c from mitochondria to the cytosol, indicating that the mitochondrial apoptotic pathway was activated. RRV infection of MA104 cells activated Bax, a proapoptotic member of the Bcl-2 family, as revealed by its conformational change. Most importantly, Bax-specific small interfering RNAs partially inhibited cytochrome c release in RRV-infected cells. Thus, mitochondrial dysfunction induced by rotavirus is Bax dependent. Apoptosis presumably leads to impaired intestinal functions, so our findings contribute to improving our understanding of rotavirus pathogenesis at the cellular level.

Cloning and characterization of Bax1 and Bax2 genes of Ctenopharyngodon idellus and evaluation of transcript expression in response to grass carp reovirus infection

“…Also, our result showed that the localization pattern of CiBax2 was different from CiBax1. It has been shown earlier that many viruses could activate Bax, such as influenza A virus, hepatitis C virus, and rotavirus (McLean et al 2009;Martin-Latil et al 2007;Benali-Furet et al 2005). In Bax -/-mice, reovirus-induced apoptosis and tissue injury were reduced compared with wild-type controls (Berens and Tylcr 2011).…”

The PI3K/Akt pathway inhibits influenza A virus-induced Bax-mediated apoptosis by negatively regulating the JNK pathway via ASK1

“…Studies have shown that JNK is required for the release of pro-apoptotic molecules such as cytochrome c from the mitochondria in response to UV irradiation (Tournier et al, 2000); the activated JNK pathway is sufficient to induce rapid cytochrome c release and apoptosis; and, furthermore, activated JNK fails to cause death in cells lacking Bax, suggesting that the JNK pathway regulates cell apoptosis through Bax (Lei et al, 2002). The regulation of mitochondria-mediated apoptosis by the JNK pathway has also been documented in reovirus, rotavirus and poliovirus infections Clarke et al, 2004;Martin-Latil et al, 2007). Based on these observations, we investigated whether the JNK pathway plays a role in regulating influenza A virus-induced Bax activation.…”

Silencing of Rotavirus NSP4 or VP7 Expression Reduces Alterations in Ca 2+ Homeostasis Induced by Infection of Cultured Cells

“…In this work, we have taken advantage of the siRNA technology to evaluate the role of NSP4 and other viral proteins (VP7 and VP4) in the changes in Ca 2ϩ homeostasis occurring in infected cells. These techniques have successfully been used to study rotavirus biology (1,3,5,7,12,21,22,25,35,36 (13). The activation of Ca 2ϩ permeability induced by infection was also reduced by the silencing of VP7; however, it was reduced to a lesser extent.…”