Hepatitis C virus is a significant public health issue and its clinical outcomes are variable. Host virus interactions play important roles in disease and treatment outcomes but the underlying Immunological mechanisms leading to spontaneous or treatment associated viral clearance are not welt understood. The studies proposed within this Hepatitis C Cooperative Research Center (HC CRC) application are focused on the innate immune mechanisms of HCV control. The proposed studies within all three projects Include both translational investigation using clinical specimens from patients with chronic hepatitis C, and in vitro expenments to evaluate mechanisms of HCV innate immune triggering, response, and infection control. These studies will rely on specialized human liver tissues, sera, plasma samples, and the associated clinical Information. Thus, we propose to establish a Clinical Core for service to all three projects in this HC CRC Program, The Liver Center at Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, is a major tertiary referral center in the Boston region and will be able to meet the requirements of the Clinical Core. The Clinical Core will serve as a central platform for the global studies in the U19 Program by providing clinical expertise and well characterized clinical specimens in support of investigating the hypotheses within each individual project of this HC CRC.

Public Health Relevance

The infrastructure provided by the Clinical Core will allow us to validate the laboratory findings using clinical samples. That will give clinical relevance to the program projects on hepatitis C and to advance our understanding ofthe immunological mechanisms of this important disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI088778-05
Application #
8648994
Study Section
Special Emphasis Panel (ZAI1-BP-M)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
5
Fiscal Year
2014
Total Cost
$91,024
Indirect Cost
$14,090
Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Chakrabarti, Arindam; Banerjee, Shuvojit; Franchi, Luigi et al. (2015) RNase L activates the NLRP3 inflammasome during viral infections. Cell Host Microbe 17:466-77
Kell, Alison; Stoddard, Mark; Li, Hui et al. (2015) Pathogen-Associated Molecular Pattern Recognition of Hepatitis C Virus Transmitted/Founder Variants by RIG-I Is Dependent on U-Core Length. J Virol 89:11056-68
Longatti, Andrea; Boyd, Bryan; Chisari, Francis V (2015) Virion-independent transfer of replication-competent hepatitis C virus RNA between permissive cells. J Virol 89:2956-61
Negash, Amina A; Gale Jr, Michael (2015) Hepatitis regulation by the inflammasome signaling pathway. Immunol Rev 265:143-55
Kell, Alison M; Gale Jr, Michael (2015) RIG-I in RNA virus recognition. Virology 479-480:110-21
Horner, Stacy M; Wilkins, Courtney; Badil, Samantha et al. (2015) Proteomic analysis of mitochondrial-associated ER membranes (MAM) during RNA virus infection reveals dynamic changes in protein and organelle trafficking. PLoS One 10:e0117963
Errett, John S; Gale, Michael (2015) Emerging complexity and new roles for the RIG-I-like receptors in innate antiviral immunity. Virol Sin 30:163-73
Wieland, Stefan; Makowska, Zuzanna; Campana, Benedetta et al. (2014) Simultaneous detection of hepatitis C virus and interferon stimulated gene expression in infected human liver. Hepatology 59:2121-30
Ireton, Reneé C; Gale Jr, Michael (2014) Pushing to a cure by harnessing innate immunity against hepatitis C virus. Antiviral Res 108:156-64
Brownell, Jessica; Bruckner, Jacob; Wagoner, Jessica et al. (2014) Direct, interferon-independent activation of the CXCL10 promoter by NF-*B and interferon regulatory factor 3 during hepatitis C virus infection. J Virol 88:1582-90

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