Herpes simplex virus is a common human pathogen that causes cold sores, fever blisters, keratitis, and encephalitis. Once infected, a person retains the virus life-long and may suffer periodic recurrence of painful lesions that take place under a variety of conditions. Thus, prevention of either primary infections or recurring HSV lesions is an important public health goal. This will likely be achieved by understanding the basic immunity mechanism to HSV infection and applying those strategies to develop effective vaccines. Recently, we observed that in the mouse model system, protective immunity to HSV infection was dampened by a class of regulatory T cells (Treg). Such cells also hampered the efficacy of certain vaccine formulations directed against the virus. However, the same type of cells were beneficial in reducing immunopathological lesions caused by HSV infection. The current proposal will define the circumstances that result in Treg induction during primary and recall immunity to HSV infection. We shall also attempt to determine if the Treg response induced by HSV infection impacts on the level of immunity to other superinfections. Finally, a number of different strategies will be used to modulate the function of Treg cells in vivo to either increase immunity to HSV or reduce the damage resulting from HSV-induced immunopathology. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI063365-01A2
Application #
7091723
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Beisel, Christopher E
Project Start
2006-02-01
Project End
2011-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
1
Fiscal Year
2006
Total Cost
$359,350
Indirect Cost
Name
University of Tennessee Knoxville
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
003387891
City
Knoxville
State
TN
Country
United States
Zip Code
37996
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Gimenez, Fernanda; Bhela, Siddheshvar; Dogra, Pranay et al. (2016) The inflammasome NLRP3 plays a protective role against a viral immunopathological lesion. J Leukoc Biol 99:647-57
Rajasagi, Naveen K; Rouse, Barry T (2016) IL-2 complex treatment amplifies CD8+ T cell mediated immunity following herpes simplex virus-1 infection. Microbes Infect 18:735-746
Bhela, Siddheshvar; Mulik, Sachin; Gimenez, Fernanda et al. (2015) Role of miR-155 in the pathogenesis of herpetic stromal keratitis. Am J Pathol 185:1073-84
Reddy, Pradeep B J; Sehrawat, Sharvan; Suryawanshi, Amol et al. (2014) An approach to control relapse of inflammatory lesions after discontinuation of primary therapy. PLoS One 9:e98051
Sharma, Shalini; Rajasagi, Naveen K; Veiga-Parga, Tamara et al. (2014) Herpes virus entry mediator (HVEM) modulates proliferation and activation of regulatory T cells following HSV-1 infection. Microbes Infect 16:648-60
Veiga-Parga, Tamara; Giménez, Fernanda; Mulik, Sachin et al. (2013) Controlling herpetic stromal keratitis by modulating lymphotoxin-alpha-mediated inflammatory pathways. Microbes Infect 15:677-87
Gimenez, Fernanda; Suryawanshi, Amol; Rouse, Barry T (2013) Pathogenesis of herpes stromal keratitis--a focus on corneal neovascularization. Prog Retin Eye Res 33:1-9
Veiga-Parga, Tamara; Sehrawat, Sharvan; Rouse, Barry T (2013) Role of regulatory T cells during virus infection. Immunol Rev 255:182-96
Veiga-Parga, Tamara; Suryawanshi, Amol; Mulik, Sachin et al. (2012) On the role of regulatory T cells during viral-induced inflammatory lesions. J Immunol 189:5924-33

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