Interferon-induced Mx proteins in host defense against tick-borne orthomyxoviruses

One of the best-studied examples of natural host resistance is the inborn resistance of A2G mice to influenza A and B virus es (reviewed in HALLER 1981; STAEHELI and HALLER 1987; STAEHELI et al. 1993). Resistance is inherited as a single, dominant trait, is specific for orthomyxoviruses, and effective against high virus doses. It is due to the interferon (IFN)-regulated MXl gene on chromosome 16 that is structurally alte red in influenza-susceptible mice (STAEHELI et al. 1988). This gene is induced upon viral infection through the action of IFN-a and -ß (STAEHELI et al. 1984) and encodes the MXl protein, a nuclear guanosine triphosphate (GTP)ase (reviewed in STAEHELI et al. 1993), which interferes with the process of influenza viral transcription in the nucleus of infected cells (KRUG et al. 1985; PAVLOVIC et al. 1992). A similar gene exists in rats (MEIER et al. 1988). Intact MX1 genes are absent in most inbred mouse strains (STAEHELI et al. 1988) but are found in wild mice (HALLER et al. 1987), showing that MXl resistance must serve a function in wild mouse populations. Most likely, rodent pathogens other than influenza A and B virus es are the primary MXl-sensitive targets (HALLER et al. 1995).