Perturbation of differentiated functions during viral infection in vivo. I. Relationship of lymphocytic choriomeningitis virus and host strains to growth hormone deficiency.
Disordered growth and glucose metabolism secondary to growth hormone deficiency is associated with persistent lymphocytic choriomeningitis virus (LCMV) infection. C3H/St, BALB/WEHI, and SWR/J mice infected at birth with LCMV:ARM carried virus in their blood and organs throughout life but only C3H/St mice developed growth hormone insufficiency. BALB/WEHI and SWR/J infected mice contained normal amounts of growth hormone in their pituitaries and a relatively small proportion of the cells containing growth hormone replicated the virus. In susceptible C3H/St mice, the disease-causing viral strains (LCMV:ARM, E-350, and Pasteur) replicated to higher titers and infected the vast majority of cells producing growth hormone in the anterior lobe of the pituitary. In contrast, LCMV strains Traub and WE replicated in far fewer growth hormone-producing cells and failed to disorder growth hormone synthesis. In another paper (Y. Riviere, R. Ahmed, P. Southern, and M. B. A. Oldstone (1985), Virology 142, 175-182) these findings are used to make reassortants between LCMV:ARM (disease positive) and LCMV:WE (disease nil) and the pathogenic effect is mapped to the small RNA segment of LCMV:ARM. Peptides cleaved by trypsin and chymotrypsin from growth hormone molecules isolated from infected cells or control cells were equivalent when examined by two-dimensional electrophoresis. Further, transfer of antibody to interferon failed to alter the growth hormone insufficiency in these mice, although it corrected LCMV-induced liver disease of BALB mice, suggesting that interferon did not play a dominant role in this disease. The selective tropism of LCMV:ARM for cells containing growth hormone over cells that contain prolactin was observed in both infected animals and in cultured GH-3 cells.
M B
MB
Oldstone
R
R
Ahmed
M J
MJ
Buchmeier
P
P
Blount
A
A
Tishon
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D002353:Carrier State; D002460:Cell Line; D002472:Cell Transformation, Viral; D006224:Cricetinae; D005260:Female; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000032:analysis / Q000172:deficiency*; D006360:Heat-Shock Proteins / Q000032:analysis; D007372:Interferons / Q000032:analysis; D007668:Kidney; D008216:Lymphocytic Choriomeningitis / Q000382:microbiology / Q000503:physiopathology; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011388:Prolactin / Q000032:analysis; D013045:Species Specificity
D000956:Antigens, Viral; D006360:Heat-Shock Proteins; D011388:Prolactin; D013006:Growth Hormone; D007372:Interferons; D005947:Glucose