To endure in hosts through their ability to establish a life-long persistent infection often associated with pathogenesis, ?-2 herpesviruses effectively antagonize host immune responses through various mechanisms. The goal of this study is to better understand how ?-2 herpesviruses evade host PCD-mediated innate immunity, with a specific focus on the viral FLICE-like inhibitor protein (FLIP), designated as vFLIP. The main hypothesis of this grant is: a novel viral immune evasion and pathogenic strategy wherein vFLIP targets NF-?B, apoptosis, and autophagy to escape host PCD-mediated innate immunity and tumor suppression, ultimately contributing to the persistence and/or pathogenesis of ?-2 herpesviruses.

Public Health Relevance

To endure in hosts through their ability to establish a life-long persistent infection often associated with pathogenesis, ?-2 herpesviruses effectively antagonize host immune responses through various mechanisms. The goal of this study is to better understand how ?-2 herpesviruses evade host programmed cell death-mediated innate immunity, with a specific focus on the viral FLICE-like inhibitor protein (FLIP), designated as vFLIP.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA031363-30
Application #
8509609
Study Section
Special Emphasis Panel (ZRG1-AARR-C (04))
Program Officer
Read-Connole, Elizabeth Lee
Project Start
1988-04-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
30
Fiscal Year
2013
Total Cost
$338,655
Indirect Cost
$122,728
Name
University of Southern California
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Rodgers, Mary A; Bowman, James W; Fujita, Hiroaki et al. (2014) The linear ubiquitin assembly complex (LUBAC) is essential for NLRP3 inflammasome activation. J Exp Med 211:1333-47
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Fan, Yihui; Mao, Renfang; Yu, Yang et al. (2014) USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase. J Exp Med 211:313-28
Lee, Myung-Shin; Jones, Tiffany; Song, Dae-Yong et al. (2014) Exploitation of the complement system by oncogenic Kaposi's sarcoma-associated herpesvirus for cell survival and persistent infection. PLoS Pathog 10:e1004412

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