In vivo and in vitro induction of MxA protein in peripheral blood mononuclear cells from patients chronically infected with hepatitis C virus.
To test whether (HCV) persistence is related to interferon (IFN) hyporesponsiveness, peripheral blood monuclear cells from 29 patients and 11 controls were studied for MxA protein expression. In vitro, only IFN-alpha (P<.001) and interleukin-2 (P<.05) induced MxA protein expression above unstimulated levels. Forty patients were treated with IFN-alpha2b. Patients showed higher basal levels of MxA protein (P<.02) and 2',5'-oligoadenylate synthase (2-5A) activity (P<.05) than controls. During therapy, MxA protein levels (P<.001) and 2-5A activity (P<.05) increased; after 1 month, MxA levels remained high, whereas 2-5A activity declined to initial levels. Increases in MxA were inversely correlated with decreases in serum alanine aminotransferase levels, and MxA induction was greater among virological responders. Thus, the IFN system seems to be activated in chronic HCV infection, but HCV appears to modulate these two components of the IFN system differentially. These results suggest that an inefficient response may contribute to virus persistence and affect the therapeutic outcome.
Department of Hepatology, Fundación Jiménez Díaz, 28040 Madrid, Spain.
M
M
Fernández
J A
JA
Quiroga
J
J
Martín
M
M
Herrero
M
M
Pardo
M A
MA
Horisberger
V
V
Carreño
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism; D000328:Adult; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D014176:Protein Biosynthesis; D011994:Recombinant Proteins
D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011994:Recombinant Proteins; D015088:2',5'-Oligoadenylate Synthetase; D019204:GTP-Binding Proteins