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American Journal of Pathology, Vol 137, 965-969, Copyright © 1990 by American Society for Investigative Pathology

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Perturbation of differentiated functions during viral infection in vivo. In vivo relationship of host genes and lymphocytic choriomeningitis virus to growth hormone deficiency

A Tishon and MB Oldstone
Department of Neuropharmacology, Research Institute of Scripps Clinic, La Jolla 92037.

Retarded growth and disordered glucose metabolism secondary to growth hormone (GH) deficiency are associated with persistent lymphocytic choriomeningitis virus (LCMV) infection of GH-producing cells in the anterior lobe of the pituitary gland. Infected C3H/ST mice, which are H- 2k haplotype, become GH deficient, and LCMV replicates in most (more than 90%) of their GH-producing cells. In contrast, BALB/WEHI and SWR/J mice, which are H-2d and H-2q, respectively, do not develop this GH deficiency, and less than 20% of their GH-producing cells are infected by virus. Yet all three strains infected at birth with LCMV strain Armstrong (ARM) carry equivalent amounts of virus in their blood, brain, heart, kidney, liver, spleen, and thymus throughout life. Of five additional H-2k murine strains tested, C3H/HEJ and CBA/N mice develop this GH-like disorder, whereas neither AKR/J, B10/BR, nor BALB/KAE mice do, indicating that the H-2K haplotype does not control the GH susceptibility. Furthermore C3H/SW mice, which have the H-2b haplotype on the C3H background, develop the disease, again negating any correlation with H-2k but inferring that the C3H background is responsible. One half of the hybrid offspring produced by crossing the C3H/ST GH-deficient strain with BALB/WEHI-resistant mice develop the disease, but the trait is not sex linked. F1 hybrid backcrosses with the susceptible C3H/ST parental strain or resistant BALB/WEHI strain indicate the involvement of more than two genes. Hence the development of a GH deficiency by LCMV-infected C3H/ST mice is not linked to the MHC haplotype, is not sex linked, and is not due to a dominant gene. Multiple genes are involved and these are related to C3H background.