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) hyporespon siveness, peripheral blood monuclear cells from 29 patients and 11 controls were studied for MxA protein expression. In vitro, only IFN-alpha (P < .00 1) and interleukin-2 (P < .05) induced MxA protein expression above unstimu lated levels. Forty patients were treated with IFN-alpha 2b. Patients showe d higher basal levels of MxA protein (P < .02) and 2',5'-oligoadenylate syn thase (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. In creases in MxA were inversely correlated with decreases in serum alanine am inotransferase levels, and MxA induction was greater among virological resp onders. Thus, the IFN system seems to be activated in chronic HCV infection , but HCV appears to modulate these two components of the IFN system differ entially. These results suggest that an inefficient response may contribute to virus persistence and affect the therapeutic outcome.