Non-structural and nucleocapsid proteins of Punta Toro virus induce apoptosis of hepatocytes through both intrinsic and extrinsic pathways

Guangyu Li, Junping Ren, Fangling Xu, Monique Ferguson

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)20-30
Number of pages11
JournalMicrobiology and Immunology
Volume54
Issue number1
DOIs
StatePublished - Jan 2010

Fingerprint

Nucleocapsid Proteins
Hepatocytes
Apoptosis
Viruses
Caspase 8
Phlebovirus
Viral Nonstructural Proteins
Bunyaviridae
Fas Ligand Protein
Caspase 9
Viral Genome
Protein S
Viral Proteins
Caspase 3
Proteins
Liver

Keywords

  • Apoptosis
  • Caspase
  • Nucleocapsid protein pathway
  • Punta Toro virus

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology

Cite this

Non-structural and nucleocapsid proteins of Punta Toro virus induce apoptosis of hepatocytes through both intrinsic and extrinsic pathways. / Li, Guangyu; Ren, Junping; Xu, Fangling; Ferguson, Monique.

In: Microbiology and Immunology, Vol. 54, No. 1, 01.2010, p. 20-30.

Research output: Contribution to journalArticle

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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.

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