MxA Gene Expression after Live Virus Vaccination: A Sensitive Marker for Endogenous Type I Interferon

Abstract

MxA gene expression is known to be regulated tightly and exclusively by type I interferons (IFNs). The kinetics of MxA gene expression was analyzed in peripheral blood mononuclear cells from 11 healthy volunteers vaccinated with the 17-D strain of yellow fever virus. A reliable induction of MxA RNA and MxA protein was found in the absence of easily detectable serum IFN activity. Thus, steady-state MxA RNA levels were elevated 8-to 30-fold above prevaccination levels on day 5 after vaccination. The average increase of MxA protein was --50-fold. In contrast, no induction of MxA RNA or MxA protein was detectable in 3 similarly vaccinated controls who were immune because of previous vaccinations. The IFN marker 2'-5'-oligoadenylate (2-5A) synthetase known to react to both type I and type II IFNs showed a similar response but did not differentiate equally well between nonimmune and immune vaccinees. P2-microglobulin and neopterin reacted poorly, remaining at low levels within the normal range. These results demonstrate that MxA gene expression is a good marker for detecting minute quantities of biologically active type I IFN during viral infections.Interferons (IFNs) are produced in response to viral infection and contribute to host defense by establishing an antiviral state in target cells [I]. Viruses induce predominantly two classes of IFNs, namely IFN-a and IFN-{1, collectively called type I IFNs [2]. It is not always possible, however, to detect circulating type I IFNs in the serum of patients most likely because type I IFNs are produced early in infection and may no longer be present in later serum samples or may not be formed in detectable quantities. For example, serum IFN is not usually found in patients with acute viral hepatitis [3,4], although IFN-induced changes occur in the liver and are suggestive oflocal IFN production and action [5]. Therefore, more reliable alternatives to direct serum IFN measurements are needed.Several assays have been developed that are based on the capacity of IFNs to induce expression of IFN-responsive genes in peripheral blood mononuclear cells (PBMC). Increased levels of an IFN-induced gene product indicate that the cells have been exposed to IFN in vivo and are respond-

Interferon type I gene expression in chronic hepatitis C

“…29 It has been shown previously that liver biopsy samples of hepatitis C patients contain elevated MxA mRNA levels along with those of other type I IFN-regulated genes. 15,30,31 To find out whether the observed expression of type I IFN-regulated genes in HCV-infected livers might be induced by intrahepatically produced IFNs, we took liver specimens from patients with chronic hepatitis C, liver disorders unrelated to viral infections, and a suspected but later excluded liver disease and analyzed the samples for the expression of type I IFN genes and that of type I IFN-regulated genes by using quantitative RT-PCR techniques (for details, see the Materials and methods section).…”

Diagnosis of Viral Infections Using Myxovirus Resistance Protein A (MxA)

“…1 Although sometimes used as viral biomarker, type I IFNs did not show good diagnostic performance because of a short half-life in body fluids. 2 The antiviral activity of type I IFNs is mediated by the induction of several proteins, including myxovirus resistance protein A (MxA). 3 MxA was first described as antiviral protein in influenza virus infection 4 and was subsequently shown to have a broad antiviral activity against a wide range of RNA and some DNA viruses.…”

Rapid and simple detection of IFN‐neutralizing antibodies in chronic hepatitis C non‐responsive to IFN‐α

“…MxA expression in PBMCs has been reported to be a highly specific and reliable marker for type I IFN bioactivity during IFN treatment or viral infections [Jakschies et al, 1994;Roers et al, 1994;Chieux et al, 1998;Meier et al, 2000;Pachner et al, 2003]. Furthermore, MxA has been used as a predictive marker of sustained antiviral response in chronically HCV-infected patients undergoing IFN therapy [Antonelli et al, 1999;Fernandez et al, 1999].…”