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Targeting macrophage Bcl6 to enhance innate resistance to influenza

Award Number: R21AI119612
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2015
PERIOD OF PERFORMANCE END DATE: 06/30/2018

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Targeting macrophage Bcl6 to enhance innate resistance to influenza - ¿ DESCRIPTION (provided by applicant): In this application, we will test the hypothesis that the Bcl6 gene, specifically in macrophages, inhibits host antiviral immunity and promotes host susceptibility to influenza virus infection. We will also explore whether the inhibition of Bcl6 function will enhance host anti-viral immunity to influenza and ameliorate severe host diseases during influenza virus infection. Two specific aims have been proposed. Specific Aim 1: To elucidate the underlying mechanisms by which Bcl6 deletion in macrophages attenuates influenza virus infection. Specific Aim 2: To determine if the inhibition of Bcl6 expression and/or function promotes macrophage IFN production and increase host resistance to influenza virus infection. The successful completion of this application will not only shed light on novel mechanisms of influenza pathogenesis and immune protection, but also open the door to developing novel therapeutic modalities against influenza infection in the near future. Relevance statement Seasonal influenza kills ~500,000 people globally and up to 50,000 people in the United States each year. In addition to seasonal outbreaks, pandemic influenza viruses occasionally emerge when humans are introduced to a virus to which they are immunologically naïve. Over the last decade, highly pathogenic avian influenza viruses (H5N1, H7N9) have emerged and recent data have highlighted the serious threat of another potential devastating influenza pandemic involving highly pathogenic virus strains. Current strategies for influenza prevention and treatment include yearly vaccination and anti-viral drugs. However, frequent changes in the surface antigens of influenza virus allow influenza viruses to escape antibody-mediated immune protection following vaccination and many circulating influenza virus strains have developed resistance to the current antiviral drugs. Thus, there is urgent need to understand the pathophysiology and the protective immune responses to influenza virus infection for the development of future preventive and therapeutic approaches. We believe that the novel method we employ here may provide alternative therapeutic modalities to those influenza virus strains that have already developed resistance to current anti-viral drugs.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2016	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	000	2	11/9/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	001	2	1/18/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$57,682
2017	2015	TRUSTEES OF INDIANA UNIVERSITY	980 INDIANA AVE RM 2232	INDIANAPOLIS	IN	46202	MARION	USA	Allergy and Infectious Diseases Research	000	1	1/18/2017	NEW	-$57,682
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $212,106 )
2016	2016	MAYO CLINIC	200 FIRST STREET, S. W.	ROCHESTER	MN	55905	OLMSTED	USA	Allergy and Infectious Diseases Research	000	2	6/30/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$212,106
														Subtotal = $212,106

Issue Date FY: 2015 ( Subtotal = $234,000 )
2015	2015	INDIANA UNIVERSITY, BLOOMINGTON	509 EAST 3RD STREET	BLOOMINGTON	IN	47405	MONROE	USA	Allergy and Infectious Diseases Research	000	1	6/24/2015	NEW	$234,000
														Subtotal = $234,000

Grand Total All Awards = $446,106

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Targeting macrophage Bcl6 to enhance innate resistance to influenza

Award Number: R21AI119612

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2015

PERIOD OF PERFORMANCE END DATE: 06/30/2018

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