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Mechanisms of Natural Killer Cell Clearance of SIV from Lymphoid Follicles

Award Number: R01AI143457
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: 06/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Mechanisms of Natural Killer Cell Clearance of SIV from Lymphoid Follicles - Despite efficient suppression of plasma viremia in HIV-infected patients on cART, replication competent virus is still recoverable from a variety of anatomic sites. A major reservoir of HIV and pathogenic SIV infection in rhesus macaques (RM) are lymph node follicles (via replication in TFH cells and viral trapping by FDC) that generally prohibit access to cytotoxic CD8+ T cells. Interestingly, nonpathogenic SIV infection of African green monkeys (AGM) exhibits high viral loads in blood and the gut mucosae, but lacks virus in lymphoid follicles. Natural killer (NK) cells provide rapid early responses to HIV/SIV infections and contribute substantially to disease modulation and vaccine protection, but the underlying mechanisms for NK cell surveillance and modulation of HIV/SIV reservoirs is unclear. Our recent research indicates that SIV can be effectively cleared from lymphoid follicles in nonpathogenic AGM but not pathogenic RM hosts and is dependent on an IL-15- dependent redistribution of NK cells to lymph node follicles and increased CXCR5 expression on AGM NK (Huot et al. Nature Medicine 2017). In this innovative proposal we will utilize three SIV-infected nonhuman primate models to test the central hypothesis that NK cells critically contribute to the reduction of SIV reservoirs. Specifically we will: (1) Determine mechanisms associated with NK cell-mediated control of SIV reservoirs; and (2) Determine mechanisms associated with NK cell failure to control SIV reservoirs in lymph nodes and associated pathogenesis. Application of these data could contribute substantially to future HIV/SIV vaccines, immunotherapeutics, or reservoir purging strategies that harness the potent antiviral potential of NK cells.


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: 2025 ( Subtotal = -$78,079 )
2025	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	000	6	4/15/2025	NON-COMPETING CONTINUATION	-$78,079
														Subtotal = -$78,079

Issue Date FY: 2023 ( Subtotal = $408,166 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Allergy and Infectious Diseases Research	000	6	11/25/2022	NON-COMPETING CONTINUATION	$408,166
														Subtotal = $408,166

Issue Date FY: 2022 ( Subtotal = $674,488 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Allergy and Infectious Diseases Research	000	5	11/18/2021	NON-COMPETING CONTINUATION	$674,488
2022	2021	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	002	4	3/28/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$78,009
2022	2020	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	2	3/28/2022	NON-COMPETING CONTINUATION	-$78,009
														Subtotal = $674,488

Issue Date FY: 2021 ( Subtotal = $697,598 )
2021	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	11/18/2020	NON-COMPETING CONTINUATION	$618,384
2021	2021	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	3	7/23/2021	NON-COMPETING CONTINUATION	-$618,384
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Allergy and Infectious Diseases Research	002	4	7/23/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$697,598
														Subtotal = $697,598

Issue Date FY: 2020 ( Subtotal = $620,422 )
2020	2020	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	11/26/2019	NON-COMPETING CONTINUATION	$620,422
														Subtotal = $620,422

Issue Date FY: 2019 ( Subtotal = $659,902 )
2019	2019	BETH ISRAEL DEACONESS MEDICAL CENTER, INC	330 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	11/15/2018	NEW	$659,902
														Subtotal = $659,902

Grand Total All Awards = $2,982,497

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Mechanisms of Natural Killer Cell Clearance of SIV from Lymphoid Follicles

Award Number: R01AI143457

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: 06/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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