MxA gene expression in peripheral blood mononuclear cells from patients infected chronically with hepatitis C virus treated with interferon-?

Abstract

Hepatitis C virus (HCV) infection causes acute and often chronic liver disease. The treatment of choice is interferon-alpha (IFN-alpha). The proportion of patients responding to therapy in terms of a sustained virological response, however, is relatively low. One possible reason for the lack of effectiveness might be neutralization of the drug by host's inhibitory factors. Recent kinetic studies suggested that high doses of IFN-alpha-, especially during the initial phase of therapy, might improve the virological response rates. Eighteen patients infected chronically with HCV were treated with IFN-alpha either at a standard dose (3 x 10(6) to 6 x 10(6) IU IFN-alpha three times weekly) for 6 to 12 months or with an intensified therapy (6 x 10(6) IU IFN-alpha daily) for at least one month. As surrogate parameter for the intracellular effect of the drug, MxA gene expression was quantified in RNA preparations from peripheral blood mononuclear cells. Beta-2-microglobulin (beta2M) concentrations were measured in serum. Serum HCV RNA titers were monitored in parallel. When compared to healthy individuals, untreated patients infected chronically with HCV were found to express 2.8-fold higher amounts of MxA specific transcripts. MxA gene expression and serum beta2M concentrations were found to be induced after administration of IFN-alpha, independent of the virological response not only during the initial phase of the intensified therapy but also over several months during standard therapy. It is concluded from these results that both early non-effectiveness of high dose IFN-alpha therapy as well as long-term non-effectiveness of standard therapy are not due to IFN-alpha inhibitory or neutralizing elements in serum.

Interferon type I gene expression in chronic hepatitis C

“…As controls, blood samples were taken from healthy volunteers instead of patients with healthy livers because the latter suffered from diseases other than hepatitis C and, therefore, might have an abnormal PBMC gene expression profile. In accordance with a previous report, 32 we found that MxA mRNA was moderately but significantly elevated in PBMCs of chronic hepatitis C patients (Figure 3a). Furthermore, RNA preparations of PBMC from hepatitis C patients contained 23-fold higher levels of IFN-a n than those from healthy individuals (Figure 3b).…”

Enhanced Expression of Interferon-Regulated Genes in the Liver of Patients with Chronic Hepatitis C Virus Infection: Detection by Suppression-Subtractive Hybridization

“…There is no evidence as to whether MxA interacts with HCV proteins during virus replication. However, MxA, like IFI-56K, is used as a surrogate marker for endogenous IFN-␣ induction and exogenous IFN-␣ application (22,28).…”

Autocrine Type I IFN and Contact with Endothelium Promote the Presentation of Influenza A Virus by Monocyte-Derived APC

“…One microgram of total RNA was synthesized into cDNA using Omniscript reverse transcriptase (Qiagen, Valencia, CA) and oligo(dT) primer (Promega, Madison, WI). MxA gene expression was amplified using MxA forward 5Ј-CTGTGGCCATACTG CGAGGA-3Ј, nt 7-26 and MxAreverse 5Ј-ACTCCTGACAGTGCCTCCAA-3Ј, nt 469-488 (480 bp) (18). Primers to detect the G3PDH gene product (402 bp) were used as an internal control.…”