Upregulation of endogenous intrahepatic interferon stimulated genes during chronic hepatitis C virus infection.
The success of interferon-alpha and ribavirin combination therapy for the treatment of chronic hepatitis C viral infection differs between patients. In an attempt to identify predictors of host response to therapy, the levels of mRNA for interferon (IFN) stimulated genes: MxA, PKR, 2'5' OAS, ISG15, and interleukin 8 (IL-8), were examined in liver by real-time RT-PCR prior to commencement of therapy. The levels of intrahepatic classical IFN stimulated genes, but not IL-8, in chronic HCV disease (n = 44) were found to be significantly upregulated (P < 0.001) compared to the control cohort (n = 12). The genotype of the infecting HCV strain did not influence IFN stimulated gene expression. These results suggest that the endogenous type 1 IFN antiviral effector pathway is broadly activated during chronic HCV disease, although the levels of mRNA for any of the IFN-stimulated genes tested did not predict the outcome of combination therapy.
MacQuillan
Gerry C
GC
Department of Medicine, The University of Western Australia, Western Australia. gerrymacquillan@hotmail.com
Mamotte
Cyril
C
Reed
William D
WD
Jeffrey
Gary P
GP
Allan
Jane E
JE
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000328:Adult; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007372:Interferons / Q000502:physiology*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008107:Liver Diseases / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D014452:Ubiquitins / Q000031:analogs & derivatives*; D015854:Up-Regulation; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D016209:Interleukin-8; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014452:Ubiquitins; D012254:Ribavirin; C074034:ISG15 protein, human; D007372:Interferons; D019892:eIF-2 Kinase; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins