The Genetic Background Modulates the Effect of the Beige Gene on Susceptibility to Cytomegalovirus Infection in Mice

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Abstract
Homozygous beige (bg/bg) mice were more susceptible to the development of fatal disease induced by murine cytomegalovirus (MCMV) than their bg/+ littermates. However, the increase in susceptibility depended on the genetic background of the strain carrying the bg gene. C57BL/6, SB/Le, DBA/2, and CBA bg/bg mice showed, respectively, 2.5-, 3.2-, 9.5-, and 18.6-fold increases in susceptibility compared with the corresponding bg/+ animals. Beige mice showed higher liver titres of MCMV than bg/+ by the 2nd or 3rd day after infection, and tissue damage was also greater. Splenic NK cells were not detected in uninfected bg/bg mice, and after virus inoculation the increment in cytotoxicity was greater in bg/+ than in bg/bg mice. However, cytotoxicity towards WEHI-164 cells was not impaired in bg/bg mice and was not augmented by MCMV. Interferon titres were also not impaired by the beige mutation. Of the strains examined, CBA had the highest endogenous levels of NK cells and were most genetically resistant to MCMV. Thus, our observation that the beige gene had the greatest effect on susceptibility in this strain suggests that NK cells are important mediators of genetically determined resistance to MCMV.