The C-terminal region of hepatitis C core protein is required for Fas-ligand independent apoptosis in Jurkat cells by facilitating Fas oligomerization.
Hepatitis C virus (HCV) is remarkable for its ability to establish persistent infection. Studies suggest that HCV core protein modulates immune responses to viral infection and can bind Fas receptor in vitro. To further examine the role of HCV core protein in Fas signaling, full-length (aa 1-192) and truncated (aa 1-152) HCV core proteins were expressed in Jurkat lymphocytes and cells were assayed for apoptotic response, caspase activation, and Fas activation. Jurkat expressing full-length but not truncated core protein exhibited ligand-independent apoptosis. Cytoplasmic targeting of truncated core protein recapitulated its ability to induce apoptosis. Activation of caspases 8 and 3 was necessary and sufficient for full-length core to induce apoptosis. Jurkat cells expressing full-length but not truncated core protein induced Fas receptor aggregation. HCV core activates apoptotic pathways in Jurkat via Fas and requires cytoplasmic localization of core. Infection of host lymphocytes by HCV may alter apoptotic signaling and skew host responses to acute infection.
Moorman
Jonathan P
JP
Department of Internal Medicine, East Tennessee State University, James H. Quillen College of Medicine, Johnson City, TN 37614, USA. moorman@mail.etsu.edu
Prayther
Deborah
D
McVay
Derek
D
Hahn
Young S
YS
Hahn
Chang S
CS
D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein; D015967:Gene Expression Regulation, Viral; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism; D020836:Protein Structure, Quaternary; D015398:Signal Transduction; D014758:Viral Core Proteins / Q000737:chemistry* / Q000378:metabolism*; D019014:fas Receptor / Q000737:chemistry / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014758:Viral Core Proteins; D019014:fas Receptor; C069130:nucleocapsid protein, Hepatitis C virus; D020169:Caspases