Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI009484-18
Application #
3124559
Study Section
Experimental Virology Study Section (EVR)
Project Start
1977-09-01
Project End
1987-11-30
Budget Start
1986-09-01
Budget End
1987-11-30
Support Year
18
Fiscal Year
1986
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; Ware, Brian C; Horton, Lucy E et al. (2018) Lymphocytic choriomeningitis virus Clone 13 infection causes either persistence or acute death dependent on IFN-1, cytotoxic T lymphocytes (CTLs), and host genetics. Proc Natl Acad Sci U S A 115:E7814-E7823
Marro, Brett S; Ware, Brian C; Zak, Jaroslav et al. (2017) Progression of type 1 diabetes from the prediabetic stage is controlled by interferon-? signaling. Proc Natl Acad Sci U S A 114:3708-3713
Hastie, Kathryn M; Igonet, Sébastien; Sullivan, Brian M et al. (2016) Crystal structure of the prefusion surface glycoprotein of the prototypic arenavirus LCMV. Nat Struct Mol Biol 23:513-521
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
Oldstone, Michael B A (2015) A Jekyll and Hyde Profile: Type 1 Interferon Signaling Plays a Prominent Role in the Initiation and Maintenance of a Persistent Virus Infection. J Infect Dis 212 Suppl 1:S31-6
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
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
Teijaro, John R; Walsh, Kevin B; Rice, Stephanie et al. (2014) Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection. Proc Natl Acad Sci U S A 111:3799-804

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