Hepatitis C virus core and envelope proteins do not suppress the host's ability to clear a hepatic viral infection.
Several hepatitis C virus (HCV) proteins have been shown in vitro to interact with host cellular components that are involved in immune regulation. However, there is a paucity of data supporting the relevance of these observations to the in vivo situation. To test the hypothesis that such an interaction suppresses immune responses, we studied a line of transgenic C57BL/6 mice that express the HCV core and envelope proteins in the liver. The potential effects of these proteins on the hepatic immune response were evaluated by challenging these mice with a hepatotropic adenovirus. Both transgenic and nontransgenic mice developed similar courses of infection and cleared the virus from the liver by 28 days postinfection. Both groups of mice mounted similar immunoglobulin G (IgG), IgG2a, interleukin-2, and tumor necrosis factor alpha responses against the virus. Additionally, BALB/c mice were able to clear infection with recombinant adenovirus that does or does not express the HCV core and envelope 1 proteins in the same manner. These data suggest that HCV core and envelope proteins do not inhibit the hepatic antiviral mechanisms in these murine experimental systems and thus favor a model in which HCV circumvents host responses through a mechanism that does not involve general suppression of intrahepatic immune responses.
Sun
J
J
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1070, USA. jisun@utmb.edu
Bodola
F
F
Fan
X
X
Irshad
H
H
Soong
L
L
Lemon
S M
SM
Chan
T S
TS
D000818:Animals; D017209:Apoptosis; D006526:Hepatitis C / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014758:Viral Core Proteins / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000502:physiology*
C087035:E1 protein, Hepatitis C virus; D014409:Tumor Necrosis Factor-alpha; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; C069130:nucleocapsid protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus