Interferon-inducible Mx gene expression in cotton rats: cloning, characterization, and expression during influenza viral infection

Abstract

Mx proteins belong to the superfamily of large GTPases with antiviral activity against a wide range of RNA viruses. In vivo, the expression of Mx genes is tightly regulated by the presence of type I interferons (IFNs), and their induction has been described during several viral infections. However, because of the absence of functional Mx genes in most common laboratory strains of mice, in vivo studies of the expression of these genes during viral infection have been hampered. We have cloned the cDNAs for the cotton rat homologs of Mx1 and Mx2 genes that encode full-length proteins. Mx1 localized in the nucleus, whereas Mx2, as its human homolog MxA, localized in the cytoplasm. The expression of Mx genes in cotton rat cells was induced by type I IFNs (IFN-alpha and IFN-beta) but induced only marginally with type II IFN (IFN-gamma). In vivo, the expression of Mx genes was dramatically augmented in lungs of cotton rats infected with influenza virus. The expression of Mx genes and protein(s) was dependent on the dose of virus and the time postinfection for the analysis. Our data present for the first time a complete analysis of the kinetics of expression of these influenza resistant genes in vivo and underscore the fidelity and sensitivity of the cotton rat model for the study of influenza viral infection.