In addition to generating an immune response with its specific antibodies and T cells, the vertebrate host can control viral infections by induction of intracellular host factors that directly interfere with viral replication. Our research focuses on a family of such intracellular proteins known as Mx proteins. One member of this family, the Mxl protein found in two strains of laboratory mice, is induced by interferon and arrests growth of influenza viruses (but not other viruses) by interfering with an early step in viral replication. We have introduced its corresponding cDNA into the germ line of Mx-negative, influenzasusceptible mice, a procedure which results in protection of the mice against fatal influenza. This procedure can be called """"""""intracellular immunization"""""""", because the mice become immune to infection, and because the antiviral principle is acting inside cells, unlike antibodies and T cells which act on cells or viruses from the outside. Proteins with homology to Mxl are expressed in organisms ranging from yeast to man, that is, they are also found in organisms for which influenza is no threat. It is possible that Mx proteins of such species have activities against other viruses. However, it is also possible that the main mission of Mx proteins is to fulfill some basic cellular function, and antiviral action is just a by product of this basic function. To test the possibility that certain Mx proteins have activities against other viruses, we have analyzed the Mx system of the rat. We found that a nuclear rat Mx protein has in fact activity not only against influenza virus, but also against vesicular stomatitis virus (VSV), a negative-stranded RNA virus against which mouse Mxl has no activity. A cytoplasmic rat Mx protein has activity only against VSV. A suggestion for a basic cellular function of Mx proteins comes from the observation that all published Mx sequences contain in their more conserved amino-terminal halves a consensus sequence characteristic of GTP-binding proteins. Thus, Mx proteins may belong to a family of GTP-binding proteins.
