Inhibition of tumor necrosis factor (TNF-alpha)-mediated apoptosis by hepatitis C virus core protein.
Hepatitis C virus (HCV) putative core protein has displayed many intriguing biological properties. Since tumor necrosis factor (TNF) plays an important role in controlling viral infection, in this study the effect of the core protein was investigated on the TNF-alpha induced apoptosis of human breast carcinoma cells (MCF7). HCV core protein when expressed inhibited TNF-alpha-induced apoptotic cell death unlike the control MCF7 cells, as determined by cell viability and DNA fragmentation analysis. Additionally, HCV core protein blocked the TNF-induced proteolytic cleavage of the death substrate poly(ADP-ribose) polymerase from its native 116-kDa protein to the characteristic 85-kDa polypeptide. Results from this study suggest that the HCV core protein plays a role in the inhibition of TNF-alpha-mediated cell death. Thus, the ability of core protein to inhibit the TNF-mediated apoptotic signaling pathway may provide a selective advantage for HCV replication, allowing for evasion of host antiviral defense mechanisms.
Ray
R B
RB
Division of Infectious Diseases and Immunology, Saint Louis University, Missouri 63110, USA.
Meyer
K
K
Steele
R
R
Shrivastava
A
A
Aggarwal
B B
BB
Ray
R
R
D017209:Apoptosis / Q000187:drug effects*; D053938:DNA Fragmentation; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014758:Viral Core Proteins / Q000235:genetics / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D011065:Poly(ADP-ribose) Polymerases