Assessing the genetic component of the susceptibility of mice to viral infections.
Laboratory mice often exhibit wide differences in susceptibility when infected experimentally with viruses. Based on such observations, experiments have been designed to investigate the determinism of these differences at the molecular level, and a few genes that play a major role in the innate mechanisms of defence of the species toward viral aggressions have been characterised. For example, the extraordinary resistance of SJL mice to experimental infections with hepatitis virus strain A59 is the consequence of a structural alteration of a cell adhesion molecule which normally binds to the spikes of the virus, allowing its entry into the cells. If the virus cannot bind to the molecule, or if the molecule is absent, epithelial cells of the intestine and liver are not infected and mice are resistant. In the same way, most--not to say all--laboratory strains of mice are susceptible to infections with orthomyxoviruses or flaviviruses because essential molecules, the synthesis of which is normally triggered by interferon, are defective in these mice. Wild mice, by contrast --probably because they are constantly exposed to natural infections--are resistant. Finally, some mouse strains resist experimental infections by the mouse cytomegalovirus 1 (MCMV-1) because, once infected, these mice synthesise a molecule at the surface of infected cells which allows immediate recognition and killing by natural killer (NK) cells. With the exuberant development of mouse genetics and the constant generation of new mutant alleles, it is likely that many more genes with an impact on the phenotype of resistance or susceptibility will be identified in the forthcoming years. These genes are probably numerous, however, and many of them presumably interact with each other and/or have additive effects. This might slow down progress in our understanding of the innate mechanism of defence.
Guénet
Jean-Louis
JL
Département de Biologie du Développement, Institut Pasteur, 75724 Paris CEDEX 15, France. jlguenet@wanadoo.fr
D020816:Amino Acid Motifs; D000818:Animals; D002043:Bunyaviridae / Q000378:metabolism; D017934:Coronavirus / Q000378:metabolism; D005416:Flavivirus / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D016678:Genome; D006518:Hepatitis Viruses / Q000378:metabolism; D006564:Herpesviridae / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000821:virology; D051379:Mice; D008815:Mice, Inbred Strains; D008957:Models, Genetic; D018146:Muromegalovirus / Q000378:metabolism; D009975:Orthomyxoviridae / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D013045:Species Specificity; D014777:Virus Diseases / Q000235:genetics*