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)
Type
Research Project (R01)
Project #
5R01CA031363-31
Application #
8698330
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
Project End
Budget Start
Budget End
Support Year
31
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Southern California
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Lee, Hye-Ra; Mitra, Jaba; Lee, Stacy et al. (2016) Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 (vIRF4) Perturbs the G1-S Cell Cycle Progression via Deregulation of the cyclin D1 Gene. J Virol 90:1139-43
Lee, Myung-Shin; Yuan, Hongfeng; Jeon, Hyungtaek et al. (2016) Human Mesenchymal Stem Cells of Diverse Origins Support Persistent Infection with Kaposi's Sarcoma-Associated Herpesvirus and Manifest Distinct Angiogenic, Invasive, and Transforming Phenotypes. MBio 7:e02109-15
Bowman, James; Rodgers, Mary A; Shi, Mude et al. (2015) Posttranslational Modification of HOIP Blocks Toll-Like Receptor 4-Mediated Linear-Ubiquitin-Chain Formation. MBio 6:e01777-15
Brulois, Kevin; Wong, Lai-Yee; Lee, Hye-Ra et al. (2015) Association of Kaposi's Sarcoma-Associated Herpesvirus ORF31 with ORF34 and ORF24 Is Critical for Late Gene Expression. J Virol 89:6148-54
Cheng, Fan; Sawant, Tanvee Vinod; Lan, Ke et al. (2015) Screening of the Human Kinome Identifies MSK1/2-CREB1 as an Essential Pathway Mediating Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication during Primary Infection. J Virol 89:9262-80
Liang, Chengyu; Oh, Byung-Ha; Jung, Jae U (2015) Novel functions of viral anti-apoptotic factors. Nat Rev Microbiol 13:7-12
Liang, Qiming; Chang, Brian; Lee, Patrick et al. (2015) Identification of the Essential Role of Viral Bcl-2 for Kaposi's Sarcoma-Associated Herpesvirus Lytic Replication. J Virol 89:5308-17
Lee, Hye-Ra; Amatya, Rina; Jung, Jae U (2015) Multi-step regulation of innate immune signaling by Kaposi's sarcoma-associated herpesvirus. Virus Res 209:39-44
Jung, Jae; Münz, Christian (2015) Immune control of oncogenic γ-herpesviruses. Curr Opin Virol 14:79-86
Seo, Gil Ju; Yang, Aerin; Tan, Brandon et al. (2015) Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway. Cell Rep 13:440-9

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