This subproject proposes the following studies to further delineate the role of persistent infections in luxury function alternation of differentiated cells: (1) Quantitation of the GH deficiency and reconstruction of GH-deficient mice; (2) Analysis of GH peptides to determine whether GH has been structurally altered during viral infection; (3) Analysis of LCMV replication; (4) Measurement of the production of autoantibodies to GH and other peptide hormones; (5) Evaluation of the hypoglycemia seen in LCMV-infected mice; (6) Evaluation of the presence and distribution of LCMV antigens on the neurons of the hypothalmus; and (7) Evaluation of the role of host factors in altering homeostasis in persistently infected mice. Each of these in vivo studies may be further extended to the diabetes mellitus model. In vitro studies planned include: (1) Investigation of alternations in production of GH and prolactin by GH-3 cells persistently infected with LCMV; (2) Evaluation of the tropism of virus for GH producing cells; and (3) Evaluation of the regulation of the GH gene, the state of the viral genome (in collaboration with Dr. Peter Southern). Alterations and production of insulin in cells persistently infected with LCMV and alterations in production of antibody by hybridomas persistently infected with LCMV will be undertaken.
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