原创力文档viral flice inhibitory protein of rhesus monkey rhadinovirus inhibits apoptosis by enhancing autophagosome formation病毒flice猕猴rhadinovirus抑制细胞凋亡的抑制蛋白促进自噬小体的形成.pdfVIP
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viral flice inhibitory protein of rhesus monkey rhadinovirus inhibits apoptosis by enhancing autophagosome formation病毒flice猕猴rhadinovirus抑制细胞凋亡的抑制蛋白促进自噬小体的形成
Viral FLICE Inhibitory Protein of Rhesus Monkey
Rhadinovirus Inhibits Apoptosis by Enhancing
Autophagosome Formation
1 1 2 1
Krit Ritthipichai , Yuchen Nan , Ioannis Bossis , Yanjin Zhang *
1 Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and Maryland Pathogen Research Institute, University of Maryland, College Park,
Maryland, United States of America, 2 Cell Biology Laboratory, VA-MD Regional College of Veterinary Medicine and Maryland Pathogen Research Institute, University of
Maryland, College Park, Maryland, United States of America
Abstract
Rhesus monkey rhadinovirus (RRV) is a gamma-2 herpesvirus closely related to human herpesvirus 8 (HHV8). RRV encodes
viral FLICE inhibitory protein (vFLIP), which has death effector domains. Little is known about RRV vFLIP. This study intended
to examine its function in apoptosis. Here we found that RRV vFLIP inhibits apoptosis induced by tumor necrosis factor-
a (TNF-a) and cycloheximide. In HeLa cells with vFLIP expression, the cleavage of poly [ADP-ribose] polymerase 1 (PARP-1)
and activities of caspase 3, 7, and 9 were much lower than those in controls. Cell viability of HeLa cells with vFLIP expression
was significantly higher than control cells after apoptosis induction. However, RRV vFLIP appears unable to induce NF-kB
signaling when tested in NF-kB reporter assay. RRV vFLIP was able to enhance cell survival under starved conditions or
apoptosis induction. At early time points after apoptosis induction, autophagosome formation was enhanced and LC3-II
level was elevated in cells with vFLIP and, when autophagy was blocked with chemical inhibitors, these cells underwent
apoptosis. Moreover, RRV latent infection of BJAB B-lymphoblastoid cells protects the cells against apoptosis by enhancing
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