Lymphocytic choriomeningitis virus selectively alters differentiated but not housekeeping functions: block in expression of growth hormone gene is at the level of transcriptional initiation.

Abstract

Persistent infection with lymphocytic choriomeningitis virus (LCMV) Armstrong strain in C3H/ST mice is associated with a growth hormone (GH) deficiency syndrome, characterized by growth retardation and low serum glucose levels (M.B.A. Oldstone et al., 1982, Science 218, 1125-1127). The syndrome is associated with a decrease in GH synthesis in the pituitary gland, in the absence of cellular injury in the pituitary or associated brain areas. In this report, we demonstrate that the decreases in steady-state synthesis of GH and its mRNA in virally infected mice is related to a 16-fold reduction in initiation of transcription of this gene. Minimal decrease, however, was demonstrated in transcriptional initiation of another pituitary gene, the precursor of thyroid simulating hormone (TSH-beta) or of the housekeeping genes, actin and pro alpha 2(I) collagen. Thus, viruses can cause disease in the absence of cytolytic or morphologic injury by selectively disrupting the synthesis of a differentiated cellular product at the level of transcriptional initiation.