TY - JOUR
T1 - Non-structural and nucleocapsid proteins of Punta Toro virus induce apoptosis of hepatocytes through both intrinsic and extrinsic pathways
AU - Li, Guangyu
AU - Ren, Junping
AU - Xu, Fangling
AU - Ferguson, Monique R.
PY - 2010/1
Y1 - 2010/1
N2 - 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 inHepG2 cells led to apoptosis in 45% of transfected cells, andwith N, 28%, on average. These levels represent a four- to an eightfold increase over cells transfected with themutated 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.
AB - 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 inHepG2 cells led to apoptosis in 45% of transfected cells, andwith N, 28%, on average. These levels represent a four- to an eightfold increase over cells transfected with themutated 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.
KW - Apoptosis
KW - Caspase
KW - Nucleocapsid protein pathway
KW - Punta Toro virus
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UR - http://www.scopus.com/inward/citedby.url?scp=75749142314&partnerID=8YFLogxK
U2 - 10.1111/j.1348-0421.2009.00178.x
DO - 10.1111/j.1348-0421.2009.00178.x
M3 - Article
C2 - 20055939
AN - SCOPUS:75749142314
SN - 0385-5600
VL - 54
SP - 20
EP - 30
JO - MICROBIOLOGY and IMMUNOLOGY
JF - MICROBIOLOGY and IMMUNOLOGY
IS - 1
ER -