the rubella virus capsid is an anti-apoptotic protein that attenuates the pore-forming ability of bax风疹病毒衣壳是一个变弱的抗凋亡蛋白的成孔能力伯灵顿.pdfVIP

The Rubella Virus Capsid Is an Anti-Apoptotic Protein that Attenuates the Pore-Forming Ability of Bax Carolina S. Ilkow1,2, Ing Swie Goping2,3,4, Tom C. Hobman 1,2,5,6* 1 Department of Cell Biology, University of Alberta, Edmonton, Canada, 2 School of Molecular and Systems Medicine, University of Alberta, Edmonton, Canada, 3 Department of Biochemistry, University of Alberta, Edmonton, Canada, 4 Department of Oncology, University of Alberta, Edmonton, Canada, 5 Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada, 6 Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Canada Abstract Apoptosis is an important mechanism by which virus-infected cells are eliminated from the host. Accordingly, many viruses have evolved strategies to prevent or delay apoptosis in order to provide a window of opportunity in which virus replication, assembly and egress can take place. Interfering with apoptosis may also be important for establishment and/or maintenance of persistent infections. Whereas large DNA viruses have the luxury of encoding accessory proteins whose primary function is to undermine programmed cell death pathways, it is generally thought that most RNA viruses do not encode these types of proteins. Here we report that the multifunctional capsid protein of Rubella virus is a potent inhibitor of apoptosis. The main mechanism of action was specific for Bax as capsid bound Bax and prevented Bax-induced apoptosis but did not bind Bak nor inhibit Bak-induced apoptosis. Intriguingly, interaction with capsid protein resulted in activation of Bax in the absence of apoptotic stimuli, however, release of cytochrome c from mitochondria and concomitant activation of caspase 3 did not occur. Accordingly, we propose that binding of capsid to Bax induces the formation of hetero-oligomers that