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Elucidating the immune response of Schreiber's bats to Lloviu virus infection in vitro and in vivo

Award Number: R21AI169646
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Elucidating the immune response of Schreiber's bats to Lloviu virus infection in vitro and in vivo - ABSTRACT Bats play an important role as natural reservoirs of numerous RNA viruses with the potential to cause significant harm to humans. In this proposal, we focus on Lloviu virus (LLOV), an under-investigated filovirus that circulates in Schreiber’s bats (Miniopterus schreibersii) in Europe. Although the pathogenic potential of LLOV for humans is not known, the close relationship of LLOV to the highly pathogenic Ebola and Marburg viruses raises concerns that a potential spillover event could lead to an outbreak among humans. LLOV was first detected Schreiber’s bats in Spain in 2002 and then again in Hungary in 2016. Sequence comparison of the Spanish and the Hungarian LLOV RNA genomes suggests that RNA editing by cellular deaminases, such as ADAR and APOBEC, might play a role in LLOV sequence diversification. In this application, we propose to explore if host-mediated RNA editing drives LLOV sequence divergence and evolution in Schreiber’s bats. In Aim 1, we propose to sample Schreiber’s bats from geographically distinct colonies and obtain LLOV sequence information from infected bats for comparative analysis. We will further develop tools based on highly sensitive droplet RT-PCR and RNA FISH that allow to determine the expression pattern of ADARs and APOBECs in LLOV-infected bat cell culture and in blood samples from infected animals. In Aim 2, based on the determined ADAR and APOBEC expression patterns, we will knockout select ADAR and/or APOBEC genes that might be involved in LLOV RNA editing in the bat cell line and examine the role of these genes in LLOV sequence diversification and viral fitness in serial passaging experiments and cell culture infection studies. Upon completion of this work, we will have revealed whether host-specific RNA editors are the drivers of LLOV evolution in bat cells. This work will contribute to our understanding of host-driven viral sequence divergence and might help assess the risk of potential LLOV spillover events from bats to humans through host-driven changes in viral sequences.


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: 2024 ( Subtotal = -$2,680 )
2024	2023	TRUSTEES OF BOSTON UNIVERSITY	85 EAST NEWTON ST # M-921	BOSTON	MA	02118	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	8/20/2024	NON-COMPETING CONTINUATION	-$2,680
														Subtotal = -$2,680

Issue Date FY: 2023 ( Subtotal = $186,300 )
2023	2023	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	1/16/2023	NON-COMPETING CONTINUATION	$186,300
														Subtotal = $186,300

Issue Date FY: 2022 ( Subtotal = $243,800 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	2/24/2022	NEW	$243,800
														Subtotal = $243,800

Grand Total All Awards = $427,420

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Elucidating the immune response of Schreiber's bats to Lloviu virus infection in vitro and in vivo

Award Number: R21AI169646

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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