The cause and pathogenesis of tissue injury in most chronic degenerative diseases of man are unclear, although some of these diseases are clearly linked with slow or persistent viral infections. The objective of work described in this continuation proposal is to study the interactions between virus, virus infected cells and the immune response in clearing virus during acute infection or, alternatively, allowing virus to escape immune surveillance and establish persistent infection. Specifically, researc ongoing or planned within this research proposal (1) evaluates the formation, identification and genetic regulation of virus-antibody immune complexes in the circulation; (2) establishes cloned cytotoxic T lymphocyte (CTL) lines in which to identify virus receptors, molecular mechanisms of membrane lysis, diversity and crossreactivity of CTLs and the structural relationship between H02 antigens and viral antigens on the plasma membrane during cytotoxic assult; (3) examines the genetic basis underlying immunopathologic disease induced by acute and persistent virus infections; (4) studies virus infection of lymphocytes as a model of persistent infection and (5) assays the ability of a persistent virus infection to affect the differentiated (""""""""luxury"""""""") function of lymphocytes, i.e., alter the production of specific antibodies made by hybridomas and abrogate the lytic activity of CTLs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI009484-26
Application #
2059572
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-09-01
Project End
1997-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
26
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Teijaro, John R; Studer, Sean; Leaf, Nora et al. (2016) S1PR1-mediated IFNAR1 degradation modulates plasmacytoid dendritic cell interferon-? autoamplification. Proc Natl Acad Sci U S A 113:1351-6
Ng, Cherie T; Mendoza, Juan L; Garcia, K Christopher et al. (2016) Alpha and Beta Type 1 Interferon Signaling: Passage for Diverse Biologic Outcomes. Cell 164:349-52
Sullivan, Brian M; Teijaro, John R; de la Torre, Juan Carlos et al. (2015) Early virus-host interactions dictate the course of a persistent infection. PLoS Pathog 11:e1004588
Ng, Cherie T; Sullivan, Brian M; Teijaro, John R et al. (2015) Blockade of interferon Beta, but not interferon alpha, signaling controls persistent viral infection. Cell Host Microbe 17:653-61
Teijaro, John R; Walsh, Kevin B; Long, James P et al. (2014) Protection of ferrets from pulmonary injury due to H1N1 2009 influenza virus infection: immunopathology tractable by sphingosine-1-phosphate 1 receptor agonist therapy. Virology 452-453:152-7
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
Oldstone, Michael B A; Rosen, Hugh (2014) Cytokine storm plays a direct role in the morbidity and mortality from influenza virus infection and is chemically treatable with a single sphingosine-1-phosphate agonist molecule. Curr Top Microbiol Immunol 378:129-47
Walsh, Kevin B; Teijaro, John R; Brock, Linda G et al. (2014) Animal model of respiratory syncytial virus: CD8+ T cells cause a cytokine storm that is chemically tractable by sphingosine-1-phosphate 1 receptor agonist therapy. J Virol 88:6281-93
Baccala, Roberto; Welch, Megan J; Gonzalez-Quintial, Rosana et al. (2014) Type I interferon is a therapeutic target for virus-induced lethal vascular damage. Proc Natl Acad Sci U S A 111:8925-30
Oldstone, Michael B A; Teijaro, John R; Walsh, Kevin B et al. (2013) Dissecting influenza virus pathogenesis uncovers a novel chemical approach to combat the infection. Virology 435:92-101

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