Interferon-α inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway

Abstract

Hepatitis C virus (HCV) persists in the majority of infected individuals and is

S-adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signalingin vitro

“…Most HCV replicons are very sensitive to IFN␣, and longer treatments for 48 hours or 72 hours result in a profound suppression of replicon RNA levels even when low concentrations of IFN␣ (e.g., 100 IU/mL or 10 IU/mL) are used. 39,45,46 Because of this high efficacy of IFN␣, we found no significant difference when adding AdoMet and betaine in 48-hour or 72-hour treatments (data not shown). We therefore confirmed the effect of AdoMet and betaine in a second system using UHCV57.3 cells infected with VSV ( Fig.…”

“…19 In these cells, HCV subgenomic RNA replication can be efficiently inhibited by IFN␣ in a time-and dose-dependent way. 39 Interestingly, we could increase the effect of IFN␣ about tenfold by adding AdoMet and betaine to IFN␣ (Fig. 7A).…”

Interferon type I gene expression in chronic hepatitis C

“…In fact, the effector protein that is most frequently found in HCV infection, MxA, has been shown not to inhibit HCV RNA replication in human hepatoma cells. 11 The finding that type I IFN mRNA molecules are easily detectable in peripheral blood samples but not in the liver of chronic hepatitis C patients might be due to the selective recruitment of peripheral cells. The liver of hepatitis C patients expresses interferon-inducible protein 10 (IP-10), a chemokine that attracts monocytes and activated T-helper cells.…”

“…10-13 Several IFNinduced proteins have been analyzed for their ability to interfere with HCV replication, but effector proteins that inhibit HCV replication have not yet been identified. 11,14 A previous approach comparing gene expression in HCV-infected liver tissues with that in noninfected livers by using the technique of suppression subtractive hybridization revealed an enhanced (ie greater than five-fold) expression of some IFN-regulated genes in the HCV-infected livers. 15 Among these are the type I IFN-regulated genes MxA, interferon inducible protein 44 (IFI-44), and interferon inducible protein 56 (IFI-56K).…”

Hepatitis C virus comes full circle: Production of recombinant infectious virus in tissue culture

“…Moreover, the replicon system has been exploited for analyses of the effect of cytokines on HCV RNA replication 46,47 and was instrumental in a recent series of elegant studies looking at host proteins involved in HCV RNA replication as well as mechanisms of evasion from innate immune responses. [48][49][50][51][52][53] Since the original reports of functional genotype 1b replicons, replicons for genotype 1a 54 and 2a 55 as well as derivatives expressing easily quantifiable marker enzymes in a separate cistron have been made to facilitate genetic studies as well as drug screening and evaluation.…”