Measles remains a major worldwide health problem due to problems with delivery, acceptance and timing of measles immunization. In addition, measles cases have been increasing in the U.S. in association with waning immunity after appropriate immunization. The primary complications of measles are pneumonia, diarrhea and postinfectious encephalomyelitis. The effect of measles on the immune system is though to be important in the development of these complications. Skin test responses and mitogen-induced lymphoproliferative responses are depressed for weeks in association with infection. At the same time, the immune response to measles virus during natural infection is effective in clearing virus from tissue and in establishing lifelong immunity to reinfection. Our studies have determined that there is immune system activation during the period of """"""""immune suppression"""""""". We have also determined that a defect in production of IL-2 contributes to the failure of T cells to proliferate in response to in vitro mitogen stimulation. To further define the relationship between measles and functional alterations in the immune system the following specific aims are proposed: (1) To identify the mononuclear cells infected by measles virus in vivo. (2) To define the in vivo state of activation and patterns of cytokine production of T cells and subsets of T cells during measles. (3) To define the state of T cell unresponsiveness and determine the similarity of this unresponsive state to that induced by lack of co-stimulatory signals from antigen presenting cells. (4) To determine the proliferative responses of T cells to alternative and supplementary stimuli. (5) To determine the role of production of inhibitors of proliferation to T cell unresponsiveness in vitro. (6) To determine whether the lack of natural killer (NK) cell activity during measles is due to lack of NK cells or to an inability of NK cells to lyse target cells. (7) To identify the immune cells present in areas of measles virus-induced inflammation and in brain during postmeasles encephalomyelitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI023047-06A1
Application #
3134916
Study Section
Immunological Sciences Study Section (IMS)
Project Start
1985-12-01
Project End
1997-04-30
Budget Start
1992-07-01
Budget End
1993-04-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Griffin, Diane E (2018) Measles Vaccine. Viral Immunol 31:86-95
Griffin, Diane E (2016) The Immune Response in Measles: Virus Control, Clearance and Protective Immunity. Viruses 8:
Shivakoti, Rupak; Hauer, Debra; Adams, Robert J et al. (2015) Limited in vivo production of type I or type III interferon after infection of macaques with vaccine or wild-type strains of measles virus. J Interferon Cytokine Res 35:292-301
Lin, Wen-Hsuan W; Pan, Chien-Hsiung; Adams, Robert J et al. (2014) Vaccine-induced measles virus-specific T cells do not prevent infection or disease but facilitate subsequent clearance of viral RNA. MBio 5:e01047
Shivakoti, Rupak; Siwek, Martina; Hauer, Debra et al. (2013) Induction of dendritic cell production of type I and type III interferons by wild-type and vaccine strains of measles virus: role of defective interfering RNAs. J Virol 87:7816-27
Okamoto, Yukari; Vricella, Luca A; Moss, William J et al. (2012) Immature CD4+CD8+ thymocytes are preferentially infected by measles virus in human thymic organ cultures. PLoS One 7:e45999
Moss, William J; Griffin, Diane E (2012) Measles. Lancet 379:153-64
Griffin, Diane E; Lin, Wen-Hsuan; Pan, Chien-Hsiung (2012) Measles virus, immune control, and persistence. FEMS Microbiol Rev 36:649-62
Ndhlovu, Zaza M; Oelke, Mathias; Schneck, Jonathan P et al. (2010) Dynamic regulation of functionally distinct virus-specific T cells. Proc Natl Acad Sci U S A 107:3669-74
Griffin, Diane E (2010) Measles virus-induced suppression of immune responses. Immunol Rev 236:176-89

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