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Preferential translation of host cell factors by hantavirus nucleocapsid protein

Award Number: R15AI126395
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: 02/06/2017
PERIOD OF PERFORMANCE END DATE: 07/31/2021

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Preferential translation of host cell factors by hantavirus nucleocapsid protein - Abstract: Hantaviruses, members of the Bunyaviridae family are enveloped negative strand RNA viruses and category A pathogens that are transmitted to humans through aerosolized excreta of infected rodent hosts. Hantaviruses have evolved a unique translation mechanism for the preferential translation of their mRNAs. This preferential translation is carried out by hantavirus nucleocapsid protein (N-protein) which specifically binds to the mRNA 5' cap and ribosomal protein S19 (RPS19), a structural component of the 40S ribosomal subunit. In addition, a trimeric N-protein molecule specifically binds to a highly conserved triplet repeat sequence (UAGUAGUAG) of the viral mRNA 5' UTR. Our results suggest that N-protein associated ribosomes are selectively loaded on viral mRNA 5' UTR to boost the translation of viral transcripts in the host cell cytoplasm where cellular transcripts are competing for the same translation machinery. Interestingly, our preliminary data shows that N-protein mediated translation strategy also favors the translation of certain host cell factors by an unknown mechanism. Using multifaceted experimental avenues we will determine the mechanism for the selective translation of certain host cell mRNAs by N-protein mediated translation strategy. We will determine whether preferential translation of host cell factors plays a role in virus replication. As antiviral response, host cells transiently shutdown the host translation machinery to create roadblocks for the synthesis of viral proteins. This antiviral response is triggered by the activation of protein kinase R (PKR), which phosphorylates its downstream target eIF2a, causing translational shutdown. Our preliminary results show that N-protein inhibits PKR activation in virus-infected cells to ensure continuous synthesis of viral proteins during the course of infection. We will test the hypothesis that N-protein requires the assistance from endogenous host cell factors to inhibit PKR antiviral response. These studies will reveal new targets for therapeutic intervention of hantavirus disease.


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 = -$3,439 )
2022	2017	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Allergy and Infectious Diseases Research	002	1	5/5/2022	NEW	-$3,439
2022	2017	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	1	3/9/2022	NEW	$6,561
2022	2017	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	3/7/2022	NEW	-$6,561
														Subtotal = -$3,439

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2017	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Allergy and Infectious Diseases Research	001	1	6/24/2021	NEW	$0
2021	2017	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	2/3/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $429,000 )
2017	2017	WESTERN UNIVERSITY OF HEALTH SCIENCES	309 E 2ND ST	POMONA	CA	91766	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	2/3/2017	NEW	$429,000
														Subtotal = $429,000

Grand Total All Awards = $425,561

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Preferential translation of host cell factors by hantavirus nucleocapsid protein

Award Number: R15AI126395

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: 02/06/2017

PERIOD OF PERFORMANCE END DATE: 07/31/2021

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