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The Role of Follicular Dendritic Cells in Maintenance of Persistent HIV

Award Number: F32AI120789
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/18/2016
PERIOD OF PERFORMANCE END DATE: 04/18/2017

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The Role of Follicular Dendritic Cells in Maintenance of Persistent HIV - ¿ DESCRIPTION (provided by applicant): Although anti-retroviral therapy (ART) effectively controls HIV-1 infection, it has several limitations including uncomfortable side effects, low accessibility, and high cost. The development of a sterilizing or functional cure would address many of these limitations. The primary obstruction to a cure is the presence of persistent, replication-competent HIV in patients on ART. Recently, several clinical trials have shown that they can target persistent HIV with small-molecule inhibitors. However, most of this work has focused on virus that is pharmacologically easily accessible in the circulatory system. The next important step is to specifically determine where reservoirs of persistent HIV exist in patients on ART so that new therapies can be targeted to these locations. This project focuses on the lymph node follicles, which are a known source of persistent HIV-1. However, the role of the individual cell types in the lymph node follicles in the persistence of HIV is not fully defined. The lymph node follicles contain follicular-dendritic cells (FDCs) that can sequester replication competent virus on their cell surface, which could then potentially infect susceptible follicular T helper cels (TFHs). Depending on whether the persistent HIV in the lymph nodes is primarily seeded by latent HIV proviruses in target cells or whether FDC-associated virions are contributing to persistence drastically affects how future strategies aimed at clearing this virus should be developed. To address this question, we have collected lymph node follicles from study participants on long-term ART and will characterize the morphology of the FDCs and TFHs using microscopy. Then, we will isolate both the FDC and the TFHs using laser-capture microdissection and will use single-genome sequencing and single-proviral sequencing to characterize the virus in these cells and determine whether HIV sequestered on FDCs acts as a reservoir of infectious virus in patients on ART and whether this virus can then disseminate to other known reservoirs of persistent HIV. By defining the role of FDCs in the persistence and dissemination of HIV in patients on long-term ART, this important work will contribute to the development of future HIV eradication clinical trials and allow them to focus and direct therapeutics to the anatomical locations that are the most relevant sources of persistent HIV. Additionally, this project will specifically address the NIAIDs area of emphasis to "Cure HIV Infection" priority one to determine if additional reservoirs of HIV infection exist.


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: 2021 ( Subtotal = -$5,625 )
2021	2017	UNIVERSITY OF SYDNEY	LEVEL 3, ADMINISTRATION BUILDING F23	THE UNIVERSITY OF SYDNEY	NSW			AUS	Allergy and Infectious Diseases Research	000	2	12/31/2020	NON-COMPETING CONTINUATION	-$5,625
														Subtotal = -$5,625

Issue Date FY: 2018 ( Subtotal = -$4,425 )
2018	2017	UNIVERSITY OF SYDNEY	L3 K07 MARGARET TELFER BUILDING	THE UNIVERSITY OF SYDNEY	NSW	2006		AUS	Allergy and Infectious Diseases Research	003	2	5/23/2018	NON-COMPETING CONTINUATION	$0
2018	2017	UNIVERSITY OF SYDNEY	L3 K07 MARGARET TELFER BUILDING	THE UNIVERSITY OF SYDNEY	NSW	2006		AUS	Allergy and Infectious Diseases Research	001	2	5/22/2018	NON-COMPETING CONTINUATION	-$4,425
														Subtotal = -$4,425

Issue Date FY: 2017 ( Subtotal = $10,050 )
2017	2017	UNIVERSITY OF SYDNEY	L 3 K07 MARGARET TELFER BUILDING	THE UNIVERSITY OF SYDNEY	NSW	2006		AUS	Allergy and Infectious Diseases Research	002	2	5/31/2017	NON-COMPETING CONTINUATION	$10,050
														Subtotal = $10,050

Issue Date FY: 2016 ( Subtotal = $11,550 )
2016	2016	UNIVERSITY OF SYDNEY-INSTITUTE FOR INTERNATIONAL HEALTH	144 BURREN STREET	NEWTON				AUS	Allergy and Infectious Diseases Research	003	1	2/15/2016	NEW	$11,550
														Subtotal = $11,550

Grand Total All Awards = $11,550

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The Role of Follicular Dendritic Cells in Maintenance of Persistent HIV

Award Number: F32AI120789

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/18/2016

PERIOD OF PERFORMANCE END DATE: 04/18/2017

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