Hepatitis C virus genotype 1b core protein does not exert immunomodulatory effects on virus-induced cellular immunity.
The hepatitis C virus (HCV) core protein is among the most conserved proteins in HCV and is known to induce sensitization of cytotoxic T lymphocytes (CTL). Therefore, it is a prime candidate for a component of a potential HCV vaccine. The HCV core protein has, however, been reported to exert multiple effects on cell functions, raising questions as to its suitability for this purpose. This question was investigated here with mice into which replication-deficient adenoviruses expressing core protein of an HCV genotype 1b isolate were injected. We show that induction of cytokines in response to the infection, infiltration of lymphocytes into the infected liver, priming of virus-specific CTL, and liver injury are not modulated by expression of the core protein in the liver. Moreover, no changes in the sensitivity to tumor necrosis factor alpha- or Fas-mediated liver injury are demonstrable. A similar lack of demonstrable effects of the core protein on immune functions has also been obtained using transgenic mice expressing another HCV genotype 1b core protein. It is concluded that the HCV core protein of genotype 1b has no modulatory effects on induction of virus-specific immune responses and may therefore be a suitable component of an HCV vaccine.
Liu
Zhang-Xu
ZX
Department of Molecular Microbiology and Immunology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
Nishida
Hiroshi
H
He
Jian-Wen
JW
Lai
Michael M C
MM
Feng
Ni
N
Dennert
Gunther
G
D000260:Adenoviruses, Human; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D008099:Liver / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology
D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; D019014:fas Receptor; C069130:nucleocapsid protein, Hepatitis C virus; D018664:Interleukin-12; D007371:Interferon-gamma; D000410:Alanine Transaminase