TY - JOUR
T1 - Perturbation of differentiated functions during viral infectionin Vivo I. Relationship of lymphocytic choriomeningitis virus and host strains to growth hormone deficiency
AU - Oldstone, Michael B.A.
AU - Ahmed, Rafi
AU - Buchmeier, Michael J.
AU - Blount, Paul
AU - Tishon, Antoinette
N1 - Funding Information:
This is Publication No. 3530-IMM from the Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, California 92037. This work was supported in part by USPHS Grants AI-09484, AG-04342, and NS-12428. The authors thank Peter Southern, Yves Riviere, and Phyllis Minick for their discussions and Gay Wilkins and Sally Booz for manuscript preparation.
PY - 1985/4/15
Y1 - 1985/4/15
N2 - 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),Virology142, 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 riot 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.
AB - 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),Virology142, 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 riot 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.
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U2 - 10.1016/0042-6822(85)90430-1
DO - 10.1016/0042-6822(85)90430-1
M3 - Article
C2 - 2414901
AN - SCOPUS:0022381995
SN - 0042-6822
VL - 142
SP - 158
EP - 174
JO - Virology
JF - Virology
IS - 1
ER -