Genetic Determinanls of Host Resistance

Genetic differences in susceptibility are most obvious when different animal species are compared. Common viral infections often tend to be less pathogenic in the natural host species than in certain exotic or introduced species. For instance, myxoma virus produces a small benign fibroma in its natural host, Sylvtlagtts brtrsiliensis, but an almost invariably fatal generalized infection in European rabbits. Likewise, most zoonoses (diseases caused by viruses of wild or domesticated animals that arc occasionally transmitted to humans, such as arenavirus, filovirus, and various arbovirus infections) cause more severe diseases in humans than in the natural hosts.

Accurate genetic data on resistance to infection are difficult to obtain in humans, because genetic, physiologic, and environmental differences are generally confounded. With inbred strains of mice, however, it has been possible to study the genetics of resistance to viral infection in some detail. Having identified a susceptible (S) and a resistant (R) strain, the LDĀ«,n assay is repeated in (S x R)F, and F2 backcrossed mice to determine whether a single gene is responsible, and whether susceptibility or resistance is dominant. Then recombinant or congenic strains can be constructed, with a common genetic background differing only in the gene in question. In this way, susceptibility or resistance of an inbred strain of mouse has sometimes been assigned to a single gene, although later work often reveals one or more additional genes which may influence susceptibility/resistance in quite different ways. For example, the response of mice to murine leukemia viruses is influenced by over a dozen known genes, whereas the response to murine cytomegalovirus is influenced by one gene that maps to the MI IC region and a second gene that is not MHC-linked but determines the titer of virus found in the spleen.

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