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Pathogenesis of and host response to chikungunya virus infection of the central nervous system

Award Number: K01OD026529
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/15/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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Pathogenesis of and host response to chikungunya virus infection of the central nervous system - Abstract The purpose of this K01 SERCA application is to provide the protected research time and mentorship necessary for Dr. Victoria Baxter, DVM, PhD, DACLAM to make the transition to independent investigator. Dr. Baxter is a veterinarian with a strong background in comparative medicine, viral immunology, and animal models of infectious disease, making her uniquely qualified for a career in translational research. Under the guidance of her mentor Dr. Mark Heise and an experienced interdisciplinary advisory committee, the training and aims outlined in this proposal will allow Dr. Baxter to expand her knowledge in viral and host genetics in order to establish a solid foundation for her own independent research program focused on understanding the pathogenesis of emerging and re-emerging viral diseases. The University of North Carolina at Chapel Hill will provide the interactive and collaborative environment necessary to support her transition to independence. Encephalitic arboviruses represent a re-emerging cause of human disease and disability, as patients who survive the initial acute disease are often left with lifelong neurological deficits. While chikungunya virus (CHIKV), an alphavirus that has recently spread to the Americas and Caribbean, typically causes a systemic disease characterized by rash and arthritis, individuals frequently develop neurological complications. Very little has been done to examine CHIKV encephalomyelitis, as no reliable small animal model currently exists. Most of the knowledge regarding the pathogenesis of alphavirus infection of the central nervous system (CNS) comes from the well-characterized mouse model of alphavirus encephalomyelitis using Sindbis virus. Outcome of CNS infection by Sindbis virus is dependent on both viral and mouse strain genetics, and CNS damage is primarily mediated by the immune response. This suggests three independent but interrelated factors drive CHIKV encephalomyelitis: viral genetics, host genetics, and the host immune system. The central hypothesis of the proposed studies is that CHIKV encephalomyelitis develops due to a combination of viral and host genetic factors, resulting in CNS damage that is primarily mediated by the host immune response rather than directly by CHIKV. This hypothesis will be tested with the following specific aims: Specific Aim #1: Determine if CHIKV genetic variation confers neurovirulence in a mouse model of CHIKV encephalomyelitis. Specific Aim #2: Elucidate the contribution of the adaptive immune system to CHIKV encephalomyelitis. Specific Aim #3: Determine if host genetic variation impacts susceptibility to CHIKV encephalomyelitis. These studies will generate valuable data that will provide a foundation for a future R01 application aimed at further elucidating mechanisms of CHIKV neuropathogenesis, and SERCA funding will provide Dr. Baxter with the skills necessary to establish similar models for examining other emerging viral diseases in the future.


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 = -$941 )
2025	2022	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Research Infrastructure Programs	000	6	12/12/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$941
														Subtotal = -$941

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Research Infrastructure Programs	002	5	6/15/2023	NON-COMPETING CONTINUATION	-$917
2023	2022	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Research Infrastructure Programs	001	6	2/15/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$118,541
2023	2022	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Research Infrastructure Programs	003	6	6/15/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$917
2023	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Research Infrastructure Programs	000	5	2/15/2023	NON-COMPETING CONTINUATION	-$118,541
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $126,222 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Research Infrastructure Programs	000	5	7/16/2022	NON-COMPETING CONTINUATION	$126,222
														Subtotal = $126,222

Issue Date FY: 2021 ( Subtotal = $126,222 )
2021	2021	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Research Infrastructure Programs	000	4	7/20/2021	NON-COMPETING CONTINUATION	$126,222
														Subtotal = $126,222

Issue Date FY: 2020 ( Subtotal = $126,222 )
2020	2020	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Research Infrastructure Programs	000	3	7/14/2020	NON-COMPETING CONTINUATION	$126,222
														Subtotal = $126,222

Issue Date FY: 2019 ( Subtotal = $126,222 )
2019	2019	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Research Infrastructure Programs	000	2	7/11/2019	NON-COMPETING CONTINUATION	$126,222
														Subtotal = $126,222

Issue Date FY: 2018 ( Subtotal = $126,222 )
2018	2018	UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL	104 AIRPORT DR STE 2200	CHAPEL HILL	NC	27599	ORANGE	USA	Research Infrastructure Programs	000	1	7/18/2018	NEW	$126,222
														Subtotal = $126,222

Grand Total All Awards = $630,169

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Pathogenesis of and host response to chikungunya virus infection of the central nervous system

Award Number: K01OD026529

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/15/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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