Interferon-regulated Mx genes are not responsive to interleukin-1, tumor necrosis factor, and other cytokines

Abstract

Accumulation of Mx gene products in cells of patients and experimental animals has been recognized as a useful marker for detecting minute quantities of biologically active interferon (IFN). Goetschy et al. (J. Goetschy, H. Zeller, J. Content, and M. A. Horisberger, J. Virol. 63:2616-2622, 1989) reported that not only IFNs but also interleukin-1 (IL-1) and tumor necrosis factor (TNF) were potent inducers of the human Mx genes. However, we observed no Mx induction in cultured human fibroblasts or in human peripheral blood mononuclear cells treated with various concentrations of IL-1 alpha or TNF-alpha. Mx induction was found in the spleens of mice treated with TNF-alpha or IL-1 alpha, but this effect could be neutralized with antibodies to murine IFN-alpha/beta. Of the other cytokines that we tested (IL-2, IL-6, and granulocyte-macrophage colony-stimulating factor), only IL-2 induced the Mx genes in peripheral blood mononuclear cells, but antibodies to human IFN-beta efficiently neutralized this effect. Our results thus indicate that IFNs are the only cytokines with intrinsic Mx-inducing activity.

Blood MxA protein as a marker for respiratory virus infections in young children

“…A surrogate marker for virus infections would be very useful to guide antimicrobial therapy decisions and discriminate virus infections from other inflammatory conditions. Myxovirus resistance protein A (MxA) is an intracellular, cytoplasmic GTPase that has activity against a wide range of viruses [2][3][4][5][6][7]. It is induced exclusively by type I and III interferons (IFNs) as a specific response to virus infections and its basal levels in healthy immunotolerant individuals are low [8,9].…”

Herpes simplex virus‐1 induces expression of a novel MxA isoform that enhances viral replication

“…1 The induction of the Mx gene as an antiviral defense of mammalian cells depends on JAK/Stat signaling and is not triggered directly by RNA viruses or doublestranded RNA. 4,5 Inhibition of RNA viruses by IFN-induced human MxA has been associated with copolymerization and sequestration of viral nucleoproteins in perinuclear complexes, which prevents genome amplification, as is observed in cells infected with LaCrosse virus and also with blocking nuclear import of capsids, as shown in studies of Thogoto virus. 6,7 Mx1 is the murine protein that corresponds to human MxA, although Mx1 has a nuclear localization signal not present in MxA.…”

Pepscan Mapping of Viral Hemorrhagic Septicemia Virus Glycoprotein G Major Lineal Determinants Implicated in Triggering Host Cell Antiviral Responses Mediated by Type I Interferon

“…1), RTG-2 cells were coincubated with paraformaldehyde-fixed EPC or EPC-gpG cells and the expression of the IS mx3 gene was assessed 24 h later, with transcription and protein levels determined by RT-qPCR and IF, respectively. The IS mx gene was chosen as a marker for IFN-mediated response because Mx proteins have proved to be a very specific and sensitive marker for type I IFN induction (39,69,79) and direct induction of this gene by rainbow trout type I IFN has been demonstrated (81). On the other hand, among the three different rainbow trout mx genes (mx1, mx2, and mx3), mx3 was selected since it is the Mx protein isoform predom-inantly expressed in RTG-2 cells in response to different type I IFN inducers (73).…”