Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG004342-06
Application #
3817784
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92037

  Publications

Oldstone, Michael B A (2014) Molecular mimicry: its evolution from concept to mechanism as a cause of autoimmune diseases. Monoclon Antib Immunodiagn Immunother 33:158-65
Priola, Suzette A; Ward, Anne E; McCall, Sherman A et al. (2013) Lack of prion infectivity in fixed heart tissue from patients with Creutzfeldt-Jakob disease or amyloid heart disease. J Virol 87:9501-10
Siggs, Owen M; Cruite, Justin T; Du, Xin et al. (2012) Disruption of copper homeostasis due to a mutation of Atp7a delays the onset of prion disease. Proc Natl Acad Sci U S A 109:13733-8
Sun, Binggui; Halabisky, Brian; Zhou, Yungui et al. (2009) Imbalance between GABAergic and Glutamatergic Transmission Impairs Adult Neurogenesis in an Animal Model of Alzheimer's Disease. Cell Stem Cell 5:624-33
Balch, William E; Morimoto, Richard I; Dillin, Andrew et al. (2008) Adapting proteostasis for disease intervention. Science 319:916-9
Trifilo, Matthew J; Sanchez-Alavez, Manuel; Solforosi, Laura et al. (2008) Scrapie-induced defects in learning and memory of transgenic mice expressing anchorless prion protein are associated with alterations in the gamma aminobutyric acid-ergic pathway. J Virol 82:9890-9
Biasini, Emiliano; Seegulam, M Esa; Patti, Brianna N et al. (2008) Non-infectious aggregates of the prion protein react with several PrPSc-directed antibodies. J Neurochem 105:2190-204
Trifilo, Matthew J; Ying, Ge; Teng, Chao et al. (2007) Chronic wasting disease of deer and elk in transgenic mice: oral transmission and pathobiology. Virology 365:136-43
Leclerc, E; Serban, H; Prusiner, S B et al. (2006) Copper induces conformational changes in the N-terminal part of cell-surface PrPC. Arch Virol 151:2103-9
Kunz, Stefan; Rojek, Jillian M; Roberts, Amanda J et al. (2006) Altered central nervous system gene expression caused by congenitally acquired persistent infection with lymphocytic choriomeningitis virus. J Virol 80:9082-92

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