Non-structural and nucleocapsid proteins of Punta Toro virus induce apoptosis of hepatocytes through both intrinsic and extrinsic pathways
Article first published online: 18 SEP 2009
© 2009 The Societies and Blackwell PUblishing Asia Pty Ltd
Microbiology and Immunology
Volume 54, Issue 1, pages 20–30, January 2010
How to Cite
Li, G., Ren, J., Xu, F. and Ferguson, M. R. (2010), Non-structural and nucleocapsid proteins of Punta Toro virus induce apoptosis of hepatocytes through both intrinsic and extrinsic pathways. Microbiology and Immunology, 54: 20–30. doi: 10.1111/j.1348-0421.2009.00178.x
- Issue published online: 23 DEC 2009
- Article first published online: 18 SEP 2009
- Received 15 July 2009; revised 13 August 2009, 27 August 2009; accepted 30 August 2009.
- nucleocapsid protein pathway;
- Punta Toro virus
Punta Toro virus (PTV; family Bunyaviridae, genus Phlebovirus) causes severe hepatic damage through brisk apoptosis of hepatocytes. In the present study, two viral proteins encoded by the S segment of the viral genome, non-structural (NSs) and nucleocapsid protein (N), were examined for their roles in apoptosis. Expression of NSs in HepG2 cells led to apoptosis in 45% of transfected cells, and with N, 28%, on average. These levels represent a four- to an eightfold increase over cells transfected with the mutated protein vectors. Caspase-3, -8 and -9 activities were increased by N protein when compared with the control NC (P < 0.05), and by NSsA and NSsB, as compared to control NSsC (P < 0.01). Treatment of the transfected cells with caspase-8 or -9 inhibitors markedly decreased apoptosis. Neutralization of TNF-α or Fas ligand had no effect on apoptosis. These results indicate that both NSs and N are responsible for causing hepatocyte apoptosis by triggering the extrinsic caspase-8 and intrinsic caspase-9 pathways.