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TAM Receptors and Virus Infection

Award Number: R01AI101400
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: 08/21/2012
PERIOD OF PERFORMANCE END DATE: 04/30/2022

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TAM Receptors and Virus Infection - PROJECT SUMMARY/ABSTRACT The receptor tyrosine kinases of the TAM family – Tyro3, Axl, and Mer – are essential regulators of infection by enveloped viruses, and Axl and Mer are especially important to arbovirus infection of cells of the central nervous system (CNS). Infection of the CNS by encephalitic arboviruses, including West Nile virus (WNV), often has devastating consequences, both acutely and after recovery, and deciphering the molecular mechanisms through which TAM receptors control virus entry, propagation, and clearance is therefore a key objective. Genetic, molecular biologic, cell biologic, and behavioral assays will be used to elucidate these mechanisms. In Aim 1, a set of new conditional mouse mutants and cell-specific Cre drivers will be used to investigate the CNS cell types through which TAM receptors control infection by WNV and two other neurotropic enveloped arboviruses - La Crosse encephalitis virus and Venezuelan equine encephalitis virus. These studies will elucidate the specific roles played by Axl and Mer in brain microvascular endothelial cells (BMECs), microglia, astrocytes, and pericytes in neuroinvasion and CNS pathogenesis by these viruses. In Aim 2, a new mouse model of learning impairment after recovery from CNS infection by WNV will be used to probe the role that Axl and Mer in microglia and astrocytes play in spatial learning and memory after infection. These experiments also will assess the role that cell-specific TAM signaling plays in synapse elimination and neurogenesis subsequent to WNV infection of the brain. In Aim 3, molecular genetics and cell-based signaling assays will be used to elucidate the molecular architecture of TAM receptor-Interferon receptor (IFNAR) interaction, which is crucial to the phenomena of Aims 1 and 2, in BMECs, microglia, macrophages, and dendritic cells. These studies will identify the signaling pathways activated by cooperative TAM receptor/INFAR signaling in these cells, and assess the ability of these interacting receptor systems to reorganize actin cytoskeletons. Together, the experiments of this proposal will guide the formulation of novel strategies for inhibiting virus entry into the CNS, attenuating virus infection of neural cells, and promoting the repair and recovery of infected neural tissues.


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: 2022 ( Subtotal = $0 )
2022	2021	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	9	9/23/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $833,577 )
2021	2021	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	9	10/23/2020	NON-COMPETING CONTINUATION	$833,577
														Subtotal = $833,577

Issue Date FY: 2020 ( Subtotal = $833,577 )
2020	2020	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	8	11/26/2019	NON-COMPETING CONTINUATION	$833,577
														Subtotal = $833,577

Issue Date FY: 2019 ( Subtotal = $833,577 )
2019	2019	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	7	11/1/2018	NON-COMPETING CONTINUATION	$833,577
														Subtotal = $833,577

Issue Date FY: 2018 ( Subtotal = $833,577 )
2018	2018	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	6	10/26/2017	NON-COMPETING CONTINUATION	$0
2018	2018	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	6	10/20/2017	NON-COMPETING CONTINUATION	$833,577
														Subtotal = $833,577

Issue Date FY: 2017 ( Subtotal = $857,077 )
2017	2017	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	5	8/2/2017	COMPETING CONTINUATION	$340,627
2017	2017	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	5	11/15/2016	COMPETING CONTINUATION	$516,450
2017	2015	SALK INSTITUTE FOR BIOLOGICAL STUDIES, SAN DIEGO, CALIFORNIA, THE	10010 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	4	2/24/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $857,077

Issue Date FY: 2015 ( Subtotal = $397,130 )
2015	2015	SALK INSTITUTE FOR BIOLOGICAL STUDIES	P.O. BOX 85800	SAN DIEGO	CA	92186	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	4	7/16/2015	NON-COMPETING CONTINUATION	$397,130
														Subtotal = $397,130

Issue Date FY: 2014 ( Subtotal = $398,050 )
2014	2014	SALK INSTITUTE FOR BIOLOGICAL STUDIES	P.O. BOX 85800	SAN DIEGO	CA	92186	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	3	7/8/2014	NON-COMPETING CONTINUATION	$398,050
														Subtotal = $398,050

Issue Date FY: 2013 ( Subtotal = $375,055 )
2013	2013	SALK INSTITUTE FOR BIOLOGICAL STUDIES	P.O. BOX 85800	SAN DIEGO	CA	92186	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	7/17/2013	NON-COMPETING CONTINUATION	$375,055
														Subtotal = $375,055

Issue Date FY: 2012 ( Subtotal = $400,000 )
2012	2012	SALK INSTITUTE FOR BIOLOGICAL STUDIES	P.O. BOX 85800	SAN DIEGO	CA	92186	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	8/21/2012	NEW	$400,000
														Subtotal = $400,000

Grand Total All Awards = $5,761,620

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TAM Receptors and Virus Infection

Award Number: R01AI101400

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: 08/21/2012

PERIOD OF PERFORMANCE END DATE: 04/30/2022

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