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Unraveling alphavirus neuroinvasion: Molecular insights from a stem cell based blood-brain barrier model

Award Number: F31AI179235
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Unraveling alphavirus neuroinvasion: Molecular insights from a stem cell based blood-brain barrier model - PROJECT SUMMARY Alphaviruses are mosquito-borne viruses that can cause arthritis and fatal encephalitis in humans with no approved therapeutics. Encephalitic alphaviruses, like Sindbis (SINV) and chikungunya (CHIKV) viruses, must cross the barriers protecting the central nervous system and therefore are neuroinvasive. The central nervous system is primarily protected by tightly connected brain microvascular endothelial cells (BMECs), pericytes, and astrocytes, which together constitute the blood-brain barrier (BBB). Genetic determinants of neuroinvasion reside in the alphavirus E2 glycoprotein and host factors that interact with the E2 glycoprotein have been identified. However, the relationship between neuroinvasive residues on E2 and the cell-specific expression of host interactors are not well characterized in the context of neuroinvasion. Our lab models the BBB by using pluripotent stem cell derived BMECs (iBMECs) that recapitulate the in vivo neuroinvasive phenotypes of alphaviruses and flaviviruses. Using this model, we have demonstrated that alphavirus neuroinvasion correlates with the ability to efficiently infect BMECs. Therefore, we hypothesize that the alphavirus E2 glycoprotein must interact with a BMEC-specific host factor to efficiently infect BMECs and cross the BBB. We will first determine how previously identified neuroinvasive E2 residues on SINV and CHIKV confer the ability to efficiently infect BMECs. Furthermore, we will identify the host factor that neuroinvasive alphaviruses hijack for efficient BMEC infection and characterize its interactions with E2. This work will elucidate virus-BBB interactions that facilitate neuropathogenesis, providing a foundation for therapeutic research. Under the fellowship training plan, I will advance my abilities in experimental design and science communication by executing, presenting, and publishing the results of this project, as well as through coursework and teaching as required by my doctoral program. My research training will take place in a rigorous and multidisciplinary scientific environment at the University of California, Los Angeles, where I have access to all the materials and expertise necessary for the completion of this project.


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: 2027 ( Subtotal = -$5,148 )
2027	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	10/27/2026	NON-COMPETING CONTINUATION	-$5,148
														Subtotal = -$5,148

Issue Date FY: 2026 ( Subtotal = -$21,567 )
2026	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	3/20/2026	NON-COMPETING CONTINUATION	-$21,567
														Subtotal = -$21,567

Issue Date FY: 2025 ( Subtotal = $45,235 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	8/20/2025	NON-COMPETING CONTINUATION	$45,235
														Subtotal = $45,235

Issue Date FY: 2024 ( Subtotal = $44,671 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	1	7/26/2024	NEW	$0
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	7/26/2024	NEW	$44,671
														Subtotal = $44,671

Grand Total All Awards = $63,191

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Unraveling alphavirus neuroinvasion: Molecular insights from a stem cell based blood-brain barrier model

Award Number: F31AI179235

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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