Disruption of Differentiated Functions during Viral Infection in Vivo
Résumé
Lymphocytic choriomeningitis virus (LCMV) Armstrong strain selectively and persistently infects the majority of growth hormone (GH) producing cells in the anterior lobe of pituitary glands of C3H/St mice but negligibly infects GH producing cells of BALB/WEHI mice (Oldstone et al., Virology 142, 175--182, 1985; Oldstone et al., Science 218, 1125--1127, 1982). Although infected GH cells remain free of structural damage, disrupted initiation of GH transcription (Klavinskis and Oldstone, J. Gen. Virol. 68, 1867--1873, 1989; Valsamakis et al., Virology 156, 214--220, 1987) occurs with a resultant decrease in the synthesis of GH, leading to a failure of growth and development (Oldstone et al., Science 218, 1125--1127, 1982). Microsatellite mapping of DNA obtained from 101 individual C3H/St x BALB/WEHI F1 x F1 mice shows that the growth failure correlates with host genes linked (P value 0.0008) on chromosome 17 just outside of the H-2D MHC site between D17 Mit24 and D17 Mit51, a distance of 2.5 cM. The genetic mapping done here excludes alpha-dystroglycan (alpha-DG), a known receptor for LCMV (Cao et al., Science 282, 2079--2081, 1998) in pathogenesis of GH disease, as alpha-DG is encoded in the mouse by a gene residing on chromosome 9 (Yotsumoto et al., Hum. Mol. Genet. 5, 1259--1267, 1996).