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EFFECT OF VIRAL ESCAPE ON MEMORY T CELL MATURATION

Award Number: R01AI043261
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: HEALTH SERVICES
PERIOD OF PERFORMANCE START DATE: 09/30/1999
PERIOD OF PERFORMANCE END DATE: 02/28/2007

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EFFECT OF VIRAL ESCAPE ON MEMORY T CELL MATURATION - DESCRIPTION (provided by applicant): Development of a memory immune response to virus infection is a critical step in the eventual control of these infections. Presence of virus-specific CD4+ T cells during the primary immune response to a virus pathogen appears to be a determining factor in whether an effective CD8 effector response is elicited. In HIV infection, where the main viral targets are HIV-specific CD4+ T ceils, the consequences for development of an effective memory are likely central for pathogenesis. In this proposal we will examine host-viral interactions occurring in the acute/early disease infection phase of HIV in 2 groups of untreated HIV infected individuals, those who do versus those who do not efficiently control viremia. Autologous plasma virus replicating before seroconversion and at a time point six month later will be completely sequenced. Variations in sequence between the original autologous virus and viral sequences used to make reference HIV peptide sets will be identified as will changes from the original autologous isolate in virus present 6 months later. Peptides spanning these variations from reference peptide sets will be synthesized. Reference and autologous peptide libraries will be used to screen lymphocytes for HIV-specific immune responses mediated by both CD4+ and CD8+ T cells using EL1SPOT and multi-parametric FACS analyses to detect antigen-specific cells that proliferate, secrete IL-2 and/or secrete IFN-.. This will survey the true breadth, magnitude and specificity of HIV-specific immunity to autologous virus and how the frequency and function of these cells changes with time to epitopes that do or do not mutate to escape immune recognition. Selected responses will be followed using tetrameric reagents to mark antigen specific cells, and phenotypic markers will be used to identify memory cells subsets and markers for function. These analyses will address the relationship between viral control and the distribution of epitope-specific CD4+ and CD8+ memory subsets in order to determine whether skewed distribution or blockage in memory cell differentiation occurs more frequently for epitopes that escape viral control compared to those that do not. Overall, we will be able to assess the importance of Ag specific CD4+ memory T cells and of viral escape in the maintenance of persistence CTL response.


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: 2006 ( Subtotal = $388,341 )
2006	2006	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC		00000		CAN	Allergy and Infectious Diseases Research	000	6	6/8/2006	NON-COMPETING CONTINUATION	$388,341
														Subtotal = $388,341

Issue Date FY: 2005 ( Subtotal = $385,894 )
2005	2005	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC		00000		CAN	Microbiology and Infectious Diseases Research	000	5	4/22/2005	NON-COMPETING CONTINUATION	$385,894
														Subtotal = $385,894

Issue Date FY: 2004 ( Subtotal = $388,732 )
2004	2004	UNIVERSITY OF MONTREAL	3850 RUE SAINT-URBAIN	MONTREAL, QUEBEC		00000		CAN	Microbiology and Infectious Diseases Research	000	4	2/23/2004	COMPETING CONTINUATION	$388,732
														Subtotal = $388,732

Issue Date FY: 2001 ( Subtotal = $291,055 )
2001	2001	UNIVERSITY OF MONTREAL	NIH (98)					USA	Microbiology and Infectious Diseases Research	000	3	9/17/2001	NON-COMPETING CONTINUATION	$291,055
														Subtotal = $291,055

Issue Date FY: 2000 ( Subtotal = $298,112 )
2000	2000	UNIVERSITY OF MONTREAL	NIH (98)					USA	Microbiology and Infectious Diseases Research	000	2	9/25/2000	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$298,112
														Subtotal = $298,112

Issue Date FY: 1999 ( Subtotal = $303,420 )
1999	1999	CLINICAL RESEARCH INSTITUTE OF MONTREAL	110 Pine Ave. W.	MONTREAL				CAN	Microbiology and Infectious Diseases Research	000	1	9/30/1999	NEW	$303,420
														Subtotal = $303,420

Grand Total All Awards = $2,055,554

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EFFECT OF VIRAL ESCAPE ON MEMORY T CELL MATURATION

Award Number: R01AI043261

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: HEALTH SERVICES

PERIOD OF PERFORMANCE START DATE: 09/30/1999

PERIOD OF PERFORMANCE END DATE: 02/28/2007

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