Functional Diversity of Mx Proteins: Variations on a Theme of Host Resistance to Infection
- Seung-Hwan Lee1 and
- Silvia M. Vidal1,2
- 1Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada
This extract was created in the absence of an abstract.
In vertebrates, host defense against pathogens is mediated by two general systems: innate and acquired immunity. Innate immunity constitutes the first line of defense, providing a rapid response by the expression of germ-line encoded proteins that preexist or are induced within hours of infection. Adaptive immunity is a slower, yet highly specific response mediated by B and T lymphocytes that confers effective and long-lasting protection against infection. Adaptive immunity is based on the generation of a large repertoire of antigen-recognition receptors by somatic gene rearrangement. Diversity has been considered the hallmark of adaptive immunity. In the last few years, however, evidence has accumulated supporting the importance of diversity (probably as a response to selective pressures) even within innate immunity (Hoffmann et al. 1999). Moreover, differences in innate immune mechanisms have been shown to be critical in host susceptibility to infection (Cooke and Hill 2001), making this an area of intense research.
The interferon-induced Mx1 protein is one of the best studied determinants of innate immunity to viral infection. In 1962, Lindenmann showed that the inbred mouse strain A2G is resistant to doses of mouse-adapted influenza virus that are lethal to other inbred strains (Lindenmann 1962). This was a particularly interesting observation because innate resistance in A2G mice was dependent on a single dominant locus, named Mx1, that was expressed in a variety of cell types ranging from macrophages to hepatocytes and was exquisitely specific for orthomyxoviruses. Subsequent studies showed that the specific resistance ofMx1+ murine cells to influenza viruses is attributable to the IFN-induced protein Mx1, and that after virus infection, the Mx1 protein is rapidly expressed in the nuclei of cells in the area where virus replication occurs, thus blocking viral spread (Arnheiter et al. 1996). The presence of a natural resistance gene to influenza was …
