The human intracellular Mx‐homologous protein is specifically induced by type I interferons

Abstract

The murine Mx-1 protein is one of the best biochemically and functionally characterized interferon (IFN)-induced proteins that is necessary, and sufficient, for providing resistance to murine cells against viral influenza infection. Recently an intracellular human protein homologous to the murine Mx-1 protein has been identified by means of a specific monoclonal antibody. The restricted induction of this intracellular protein in human mononuclear cells (MNC) by various cytokines was investigated. MNC from 26 of 28 healthy people and 35 of 36 cancer patients before IFN-α therapy had no detectable Mx-homologous protein. Incubation of human MNC with IFN-α and IFN-β for 24 h at different concentrations led to a dose-dependent induction of the Mx-homologous protein. All IFN-α or IFN-β preparations tested were equally effective in eliciting this intracellular protein. IFN-γ induced only 1% of the Mx amount elicited by type-1 IFN compared on a weight basis. Neither interleukin (IL) 1 nor IL 3, IL 4, IL 5, IL 6, tumor necrosis factor-α/β, granulocyte colony-stimulating factor (CSF) or granulocyte macrophage-CSF at any of the concentrations tested were capable of eliciting any detectable amount of the Mx homolog, while IL 2 was a poor Mx-homologous protein inducer. In the presence of high-titered IFN-α antisera both IL 2 and IFN-γ were unable to stimulate this protein, proving that IFN-γ and IL 2 indirectly induce the Mx homolog via IFN-α. Therefore, the human Mx-homologous protein is a strictly by type I IFN-regulated protein in human peripheral blood lymphocytes.